Disease Information

General Information of the Disease (ID: DIS00096)

Name	Prostate cancer
ICD	ICD-11: 2C82
Resistance Map

Type(s) of Resistant Mechanism of This Disease

ADTT: Aberration of the Drug's Therapeutic Target

EADR: Epigenetic Alteration of DNA, RNA or Protein

IDUE: Irregularity in Drug Uptake and Drug Efflux

MRAP: Metabolic Reprogramming via Altered Pathways

RTDM: Regulation by the Disease Microenvironment

UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s)

14 drug(s) in total

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Doxorubicin

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Metabolic Reprogramming via Altered Pathways (MRAP)			Click to Show/Hide
Key Molecule: Pyruvate kinase L/R (PKLR)				[1]
Metabolic Type	Mitochondrial metabolism
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Doxorubicin			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate cancer
The Studied Tissue	Blood
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 5.48E-20 Fold-change: 7.15E-01 Z-score: 1.03E+01
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Metabolic pathways		Activation	hsa01100
	Transcriptional misregulation in cancer		Activation	hsa05202
In Vivo Model	6-week-old male nude mice, with LASCPC01 cells			Mice
Experiment for Molecule Alteration	qRT-PCR; Western blot analysis
Experiment for Drug Resistance	Tumor volume assay
Mechanism Description	Our study found significant correlations between ROMO1 and NE-related gene upregulation in PCa after ADT, which may have been caused by the nuclear translocation of PKLR and its interaction with the MYCN/MAX complex to promote ROMO1 and NE marker expression. Importantly, we found that this interaction decreased after treatment with a putative MYCN inhibitor. These data suggest that PKLR may also act as a transcription cofactor of MYCN, in addition to acting as a kinase, similar to PKM2, which acts as a transcription cofactor to activate hypoxia-inducible factor-1A (HIF1A) to promote castration resistance [22].
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: PCGEM1 prostate-specific transcript (PCGEM1)				[15]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Doxorubicin			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate adenocarcinoma
The Studied Tissue	Prostate
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 1.91E-09 Fold-change: 1.52E+00 Z-score: 6.12E+00
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
Experiment for Molecule Alteration	Northern blotting analysis
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	PCGEM1overexpression in LNCaP cell culturemodel results in the inhibition of apoptosis induced by doxorubicin (DOX). Induction of p53 and p21Waf1/Cip1by DOX were delayed in LNCaP cells stably overexpressing PCGEM1(LNCaP-PCGEM1cells) compared tocontrol LNCaP cells.
Key Molecule: LOXL1 antisense RNA 1 (LOXL1-AS1)				[27]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Doxorubicin			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate adenocarcinoma
The Studied Tissue	Prostate
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 4.33E-01 Fold-change: -3.94E-02 Z-score: -7.86E-01
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell migration		Activation	hsa04670
	Cell proliferation		Activation	hsa05200
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay
Mechanism Description	LncRNA LOXL1-AS1/miR-let-7a-5p/EGFR-related pathway regulates the doxorubicin resistance of prostate cancer DU-145 cells.
Key Molecule: hsa-let-7a-5p				[27]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Doxorubicin			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell migration		Activation	hsa04670
	Cell proliferation		Activation	hsa05200
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay
Mechanism Description	LncRNA LOXL1-AS1/miR-let-7a-5p/EGFR-related pathway regulates the doxorubicin resistance of prostate cancer DU-145 cells.
Key Molecule: Lactate dehydrogenase A (LDHA)				[37]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Doxorubicin			Drug Info
Molecule Alteration	Expression		T227M	Molecule Info
Mechanism Description	7928 genes were identified as genes related to tumor progression and metastasis. Of these, 7 genes were found to be associated with PCa prognosis. The scRNA-seq and TCGA data showed that the expression of LDHA was higher in tumors and associated with poor prognosis of PCa. In addition, upregulation of LDHA in PCa cells induces osteoclast differentiation. Additionally, high LDHA expression was associated with resistance to Epirubicin, Elliptinium acetate, and doxorubicin. Cellular experiments demonstrated that LDHA knockdown inhibited doxorubicin resistance in PCa cells.
Irregularity in Drug Uptake and Drug Efflux (IDUE)			Click to Show/Hide
Key Molecule: Multidrug resistance-associated protein 1 (MRP1)				[19]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Doxorubicin			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate cancer
The Studied Tissue	Prostate
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 8.18E-07 Fold-change: 1.22E-01 Z-score: 6.14E+00
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
	22RV1 cells	Prostate	Homo sapiens (Human)	CVCL_1045
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	However, higher concentrations of probenecid (500 uM) failed to demonstrate a chemosensitizing effect. Consistent with this lower chemosensitizing efficacy in higher-concentration probenecid treatment, we observed that the expression of ABCG2, a drug-efflux transporter, increased in a dose-dependent manner following probenecid treatment. Thus, probenecid could enhance the chemosensitivity of 3D-cultured prostate cancer cells, but not at higher concentr.
Key Molecule: ATP-binding cassette sub-family C2 (ABCC2)				[19]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Doxorubicin			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
	22RV1 cells	Prostate	Homo sapiens (Human)	CVCL_1045
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	However, higher concentrations of probenecid (500 uM) failed to demonstrate a chemosensitizing effect. Consistent with this lower chemosensitizing efficacy in higher-concentration probenecid treatment, we observed that the expression of ABCG2, a drug-efflux transporter, increased in a dose-dependent manner following probenecid treatment. Thus, probenecid could enhance the chemosensitivity of 3D-cultured prostate cancer cells, but not at higher concentr.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Epidermal growth factor receptor (EGFR)				[27]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Doxorubicin			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate cancer
The Studied Tissue	Prostate
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 7.43E-04 Fold-change: -1.42E-01 Z-score: -3.79E+00
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell migration		Activation	hsa04670
	Cell proliferation		Activation	hsa05200
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
Experiment for Molecule Alteration	Western blot analysis; RT-qPCR
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay
Mechanism Description	LncRNA LOXL1-AS1/miR-let-7a-5p/EGFR-related pathway regulates the doxorubicin resistance of prostate cancer DU-145 cells.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Irregularity in Drug Uptake and Drug Efflux (IDUE)			Click to Show/Hide
Key Molecule: ATP-binding cassette sub-family B5 (ABCB5)				[30]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]
Sensitive Drug	Doxorubicin			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate cancer
The Studied Tissue	Prostate
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 2.06E-05 Fold-change: -1.09E-01 Z-score: -4.94E+00
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	DU-145Nox1 cells	Prostate	Homo sapiens (Human)	CVCL_0105
Experiment for Molecule Alteration	Immunohistochemistry assay
Experiment for Drug Resistance	Annexin V staining assay
Mechanism Description	In DU-145Nox1 tumor spheroids, expression of HIF-1alpha as well as P-gp was significantly decreased as compared to DU-145 spheroids, which resulted in an increased retention of the anticancer agent doxorubicin. Pretreatment with the free radical scavengers vitamin E and vitamin C increased the expression of P-gp as well as HIF-1alpha in Nox-1-overexpressing cells, whereas no effect of free radical scavengers was observed on mdr-1 mRNA expression.

Bicalutamide

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Drug Resistance Data Categorized by Their Corresponding Mechanisms

Regulation by the Disease Microenvironment (RTDM)

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Key Molecule: Protocadherin beta-9 (PCDHB9)

[3]

Resistant Disease

Prostate cancer [ICD-11: 2C82.0]

Resistant Drug

Bicalutamide

Drug Info

Molecule Alteration

Expression

Up-regulation

Molecule Info

Differential expression of the molecule in resistant disease

Classification of Disease

Prostate cancer [ICD-11: 2C82]

The Specified Disease

Prostate cancer

The Studied Tissue

Prostate

The Expression Level of Disease Section Compare with the Healthy Individual Tissue

p-value: 1.81E-02

Fold-change: 7.01E-02

Z-score: 2.42E+00

Experimental Note

Identified from the Human Clinical Data

In Vitro Model

LN229 cells

Brain

Homo sapiens (Human)

CVCL_0393

Experiment for
Drug Resistance

MTT assay

Mechanism Description

Bicalutamide has been widely used as a first-line treatment for PCa. Although patients initially show a favorable response to bicalutamide treatment, PCa eventually acquires bicalutamide resistance. Several factors have been shown to be involved in bicalutamide resistance. However, the mechanism of bicalutamide resistance is not fully understood. In this study, the knockdown of protocadherin B9 reduced nuclear AR translocation and bicalutamide resistance in androgen-dependent LNCaP cells in the presence of DHT. The overexpression of protocadherin B9 had no effect on bicalutamide resistance in androgen-independent DU145 cells. These results further indicate that protocadherin B9 is involved in bicalutamide resistance through the modulation of AR signaling. Taken together, our findings suggest that protocadherin B9 targeted therapy could be more effective therapy than bicalutamide alone for patients with PCa.

Aberration of the Drug's Therapeutic Target (ADTT)

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Key Molecule: Androgen receptor (AR)

[42]

Resistant Disease

Prostate cancer [ICD-11: 2C82.0]

Resistant Drug

Bicalutamide

Drug Info

Molecule Alteration

Missense mutation

p.W742L (c.2225G>T)

Molecule Info

Wild Type Structure

Method: X-ray diffraction

Resolution: 2.07 Å

PDB: 5CJ6

Mutant Type Structure

Method: X-ray diffraction

Resolution: 1.70 Å

PDB: 2AX8

Download The Information of Sequence

Download The Structure File

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Experimental Note

Identified from the Human Clinical Data

Key Molecule: Androgen receptor (AR)

[42]

Resistant Disease

Prostate cancer [ICD-11: 2C82.0]

Resistant Drug

Bicalutamide

Drug Info

Molecule Alteration

Missense mutation

p.W742C (c.2226G>T)

Molecule Info

Experimental Note

Identified from the Human Clinical Data

Metabolic Reprogramming via Altered Pathways (MRAP)

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Key Molecule: Squalene epoxidase (SQLE)

[43]

Metabolic Type

Lipid metabolism

Resistant Disease

Prostate cancer [ICD-11: 2C82.0]

Resistant Drug

Bicalutamide

Drug Info

Molecule Alteration

Expression

Up-regulation

Molecule Info

Experimental Note

Revealed Based on the Cell Line Data

In Vivo Model

Male NOD/SCID nude mice, With LNCaP, C4-2B, and C4-2B_shSQLE cells

Mice

Experiment for
Molecule Alteration

qRT-PCR; Western blot analysis

Experiment for
Drug Resistance

Tumor volume assay

Mechanism Description

In our study, we found that the expression level of SQLE was significantly increased in bicalutamide-resistant-C4-2B cells compared to LNCaP cells. SQLE knockdown partly restored the sensitivity of drug-resistant cells to bicalutamide and reduced lymph node metastasis by inhibiting fatty acid oxidation in mitochondria. We also found that terbinafine, the specific inhibitor of SQLE, can enhance the sensitivity of prostate cancer cells to bicalutamide.

Docetaxel

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Metabolic Reprogramming via Altered Pathways (MRAP)			Click to Show/Hide
Key Molecule: L-glutamine amidohydrolase (GLS)				[4]
Metabolic Type	Glutamine metabolism
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate cancer
The Studied Tissue	Prostate
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 1.08E-01 Fold-change: 5.66E-02 Z-score: 1.67E+00
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	293 T cells	Blood	Homo sapiens (Human)	N.A.
	DU145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	PC-3 cells	Bone	Homo sapiens (Human)	CVCL_0035
Experiment for Molecule Alteration	qRT-PCR; Western blot analysis
Experiment for Drug Resistance	Cell viability assay
Mechanism Description	Mechanistically, Gln deprivation reduced OXPHOS and ATP levels, causing a disturbance in cell cycle progression. Genetic and chemical inhibition of the Gln-metabolism key protein GLS1 could validate the Gln deprivation results, thereby representing a valid therapeutic target. Moreover, immunohistological investigation of GLS1 revealed a high-expressing GLS1 subgroup post-docetaxel failure, exhibiting low overall survival. This subgroup presents an intriguing opportunity for targeted therapy focusing on glutamine metabolism.
Key Molecule: Hexokinase 2 (HK2)				[53]
Metabolic Type	Glucose metabolism
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	SUMOylated		K315	Molecule Info
Experimental Note	Identified from the Human Clinical Data
In Vivo Model	Prostate cancer patients			Homo Sapiens
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Cell prognosis assay
Mechanism Description	Here, we report that SUMOylation regulates the binding of hexokinase 2 to mitochondria. We find that hexokinase 2 can be SUMOylated at K315 and K504.
Key Molecule: AKT serine/threonine kinase 1 (AKT1)				[54]
Metabolic Type	Glucose metabolism
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	.		.	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	PI3K-Akt signaling pathway		Activation	hsa04151
In Vitro Model	Human prostate cancer LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
Mechanism Description	Our evidence revealed that Icariin-Curcumol attenuated DTX resistance through modulation of the PI3K-Akt pathway and the Warburg effect and that Icariin-Curcumol and DTX have synergistic effects.
Key Molecule: Forkhead box G1 (FOXG1)				[55]
Metabolic Type	Mitochondrial metabolism
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	DU145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
	PC-3 cells	Bone	Homo sapiens (Human)	CVCL_0035
	RWPE-1 cells	Prostate	Homo sapiens (Human)	CVCL_3791
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	FOXG1 exhibited high expression in PCa tissues and cell lines. Knockdown of FOXG1 inhibited the proliferation, migration, and invasion of PCa cells, while FOXG1 overexpression had the opposite effect and promoted OXPHOS levels. The addition of an OXPHOS inhibitor prevented this outcome. Finally, SSd was shown to suppress FOXG1 expression and reverse docetaxel resistance in PCa cells through the OXPHOS pathway.
Key Molecule: AKT serine/threonine kinase 1 (AKT1)				[54]
Metabolic Type	Glucose metabolism
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	.		.	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	PI3K-Akt signaling pathway		Activation	hsa04151
In Vivo Model	Male BALB/c nude mice, LNCaP cells			Mice
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	Our evidence revealed that Icariin-Curcumol attenuated DTX resistance through modulation of the PI3K-Akt pathway and the Warburg effect and that Icariin-Curcumol and DTX have synergistic effects.
Key Molecule: Hexokinase 2 (HK2)				[53]
Metabolic Type	Glucose metabolism
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	SUMOylated		K315	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Cell viability assay
Mechanism Description	Here, we report that SUMOylation regulates the binding of hexokinase 2 to mitochondria. We find that hexokinase 2 can be SUMOylated at K315 and K492.
Key Molecule: Hexokinase 2 (HK2)				[53]
Metabolic Type	Glucose metabolism
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	SUMOylated		K315	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	22Rv-1 cells	Prostate	Homo sapiens (Human)	CVCL_1045
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Cell viability assay
Mechanism Description	Here, we report that SUMOylation regulates the binding of hexokinase 2 to mitochondria. We find that hexokinase 2 can be SUMOylated at K315 and K493.
Key Molecule: Hexokinase 2 (HK2)				[53]
Metabolic Type	Glucose metabolism
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	SUMOylated		K315	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	PC-3 cells	Bone	Homo sapiens (Human)	CVCL_0035
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Cell viability assay
Mechanism Description	Here, we report that SUMOylation regulates the binding of hexokinase 2 to mitochondria. We find that hexokinase 2 can be SUMOylated at K315 and K494.
Key Molecule: Hexokinase 2 (HK2)				[53]
Metabolic Type	Glucose metabolism
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	SUMOylated		K315	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	293 T cells	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Cell viability assay
Mechanism Description	Here, we report that SUMOylation regulates the binding of hexokinase 2 to mitochondria. We find that hexokinase 2 can be SUMOylated at K315 and K495.
Key Molecule: Hexokinase 2 (HK2)				[53]
Metabolic Type	Glucose metabolism
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	SUMOylated		K492	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Cell viability assay
Mechanism Description	Here, we report that SUMOylation regulates the binding of hexokinase 2 to mitochondria. We find that hexokinase 2 can be SUMOylated at K315 and K496.
Key Molecule: Hexokinase 2 (HK2)				[53]
Metabolic Type	Glucose metabolism
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	SUMOylated		K492	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	22Rv-1 cells	Prostate	Homo sapiens (Human)	CVCL_1045
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Cell viability assay
Mechanism Description	Here, we report that SUMOylation regulates the binding of hexokinase 2 to mitochondria. We find that hexokinase 2 can be SUMOylated at K315 and K497.
Key Molecule: Hexokinase 2 (HK2)				[53]
Metabolic Type	Glucose metabolism
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	SUMOylated		K492	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	PC-3 cells	Bone	Homo sapiens (Human)	CVCL_0035
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Cell viability assay
Mechanism Description	Here, we report that SUMOylation regulates the binding of hexokinase 2 to mitochondria. We find that hexokinase 2 can be SUMOylated at K315 and K498.
Key Molecule: Hexokinase 2 (HK2)				[53]
Metabolic Type	Glucose metabolism
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	SUMOylated		K492	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	293 T cells	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Cell viability assay
Mechanism Description	Here, we report that SUMOylation regulates the binding of hexokinase 2 to mitochondria. We find that hexokinase 2 can be SUMOylated at K315 and K499.
Key Molecule: Pyruvate kinase muscle isozyme 1 (PKM1)				[56]
Metabolic Type	Mitochondrial metabolism
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	PC-3/PTXR cells	Prostate	Homo sapiens (Human)	CVCL_0035
Experiment for Molecule Alteration	Expression profiles
Experiment for Drug Resistance	Cell viability assay
Mechanism Description	The overexpression of PKM1 resulted in resistance of the parental cells to 5-FU and oxaliplatin.
Key Molecule: Hexokinase 2 (HK2)				[53]
Metabolic Type	Glucose metabolism
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	SUMOylated		K315	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
In Vivo Model	Male BALB/c nude mice, PC3 cells			Mice
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Tumor volume assay
Mechanism Description	Here, we report that SUMOylation regulates the binding of hexokinase 2 to mitochondria. We find that hexokinase 2 can be SUMOylated at K315 and K500.
Key Molecule: Hexokinase 2 (HK2)				[53]
Metabolic Type	Glucose metabolism
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	SUMOylated		K315	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
In Vivo Model	Male BALB/c nude mice, 22Rv1 cells			Mice
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Tumor volume assay
Mechanism Description	Here, we report that SUMOylation regulates the binding of hexokinase 2 to mitochondria. We find that hexokinase 2 can be SUMOylated at K315 and K501.
Key Molecule: Hexokinase 2 (HK2)				[53]
Metabolic Type	Glucose metabolism
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	SUMOylated		K492	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
In Vivo Model	Male BALB/c nude mice, PC3 cells			Mice
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Tumor volume assay
Mechanism Description	Here, we report that SUMOylation regulates the binding of hexokinase 2 to mitochondria. We find that hexokinase 2 can be SUMOylated at K315 and K502.
Key Molecule: Hexokinase 2 (HK2)				[53]
Metabolic Type	Glucose metabolism
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	SUMOylated		K492	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
In Vivo Model	Male BALB/c nude mice, 22Rv1 cells			Mice
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Tumor volume assay
Mechanism Description	Here, we report that SUMOylation regulates the binding of hexokinase 2 to mitochondria. We find that hexokinase 2 can be SUMOylated at K315 and K503.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Metastasis-associated protein MTA1 (MTA1)				[7]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate cancer
The Studied Tissue	Prostate
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 1.16E-01 Fold-change: 4.86E-02 Z-score: 1.64E+00
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	MTA1 signaling pathway		Activation	hsa05206
In Vitro Model	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
Experiment for Molecule Alteration	Promoter reporter assay; Western blot analysis
Experiment for Drug Resistance	ELISA; MTT assay
Mechanism Description	Regulation of docetaxel sensitivity in prostate cancer cells by hsa-miR125a-3p via modulation of metastasis-associated protein 1 signaling, MTA1 is a direct target of hsa-mir125a-3p in pca cells.
Key Molecule: Apoptosis regulator Bcl-2 (BCL2)				[8]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate cancer
The Studied Tissue	Prostate
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 1.29E-02 Fold-change: 4.09E-02 Z-score: 2.60E+00
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell proliferation		Activation	hsa05200
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
	22RV1 cells	Prostate	Homo sapiens (Human)	CVCL_1045
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Acid phosphatase assay
Mechanism Description	miR-34a regulates BCL-2 and may, in part, regulate response to docetaxel. miR-34a was significantly decreased in prostate cancer versus normal tissues; in biochemical recurrence versus non-recurrence tissue and in metastatic versus primary disease prostate tissue. We confirmed BCL-2 as a target of miR-34a, by manipulating miR-34a expression in our parent and docetaxel resistant cell lines and subsequently assessing BCL-2 levels. Specifically, upon inhibition of miR-34a in sensitive parent cells (PC3 and 22Rv1) we observed an increase in BCL-2 expression, whereas mimicking miR-34a expression in docetaxel-resistant cells (PC3RD and 22Rv1RD) resulted in decreased BCL-2 expression.
Key Molecule: A-kinase anchor protein 12 (AKAP12)				[17]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate cancer
The Studied Tissue	Prostate
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 7.51E-02 Fold-change: 1.30E-01 Z-score: 1.86E+00
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell invasion		Activation	hsa05200
	Cell proliferation		Activation	hsa05200
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay; Scratch Wound healing assay; Transwell Invasion assay; Flow cytometry assay
Mechanism Description	Knockdown of MALAT1 in DTX-resistant PCa cells up-regulated miR-145-5p as well as suppressed AkAP12 expression, further inhibited cell viability and induced apoptosis.
Key Molecule: Tumor necrosis factor ligand superfamily member 10 (TNFSF10)				[21]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate cancer
The Studied Tissue	Prostate
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 9.66E-01 Fold-change: -7.23E-04 Z-score: -4.34E-02
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell proliferation		Activation	hsa05200
In Vitro Model	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
	VCaP cells	Prostate	Homo sapiens (Human)	CVCL_2235
	LTAD cells	Prostate	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Western blot analysis; Immunohistochemistry assay
Experiment for Drug Resistance	TUNEL assay; MTS assay
Mechanism Description	Androgen-induced Long Noncoding RNA (LncRNA) SOCS2-AS1 Promotes Cell Growth and Inhibits Apoptosis in Prostate Cancer Cells.suppressor of cytokine signaling 2-antisense transcript 1 (SOCS2-AS1), the expression of which was higher in castration-resistant prostate cancer model cells.SOCS2-AS1 promoted castration-resistant and androgen-dependent cell growth. We found that SOCS2-AS1 knockdown up-regulated genes related to the apoptosis pathway, including tumor necrosis factor superfamily 10 (TNFSF10), and sensitized prostate cancer cells to docetaxel treatment. Moreover, we also demonstrated that SOCS2-AS1 promotes androgen signaling by modulating the epigenetic control for AR target genes including TNFSF10 These findings suggest that SOCS2-AS1 plays an important role in the development of castration-resistant prostate cancer by repressing apoptosis.
Key Molecule: Protein transport protein Sec23A (SEC23A)				[28]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate cancer
The Studied Tissue	Prostate
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 2.83E-01 Fold-change: -4.00E-02 Z-score: -1.10E+00
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay; Annexin V-PE Apoptosis assay
Mechanism Description	miR375 induces docetaxel resistance in prostate cancer by targeting SEC23A and YAP1.
Key Molecule: Tumor protein p73 (TP73)				[31]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate cancer
The Studied Tissue	Prostate
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 4.84E-04 Fold-change: -1.18E-01 Z-score: -4.02E+00
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Luciferase reporter assay; Western blot analysis
Experiment for Drug Resistance	MTT assay; Flow cytometric analysis
Mechanism Description	microRNA-323 upregulation promotes prostate cancer growth and docetaxel resistance by repressing p73.
Key Molecule: Transcriptional coactivator YAP1 (YAP1)				[28]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay; Annexin V-PE Apoptosis assay
Mechanism Description	miR375 induces docetaxel resistance in prostate cancer by targeting SEC23A and YAP1.
Key Molecule: Clusterin (CLU)				[49]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell colony		Activation	hsa05200
	Cell viability		Activation	hsa05200
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay
Mechanism Description	miR-195 improved the sensitivity of resistant PC cells to DOC by suppressing CLU.
Key Molecule: Bcl-2-like protein 2 (BCL2L2)				[46]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell proliferation		Inhibition	hsa05200
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
	RWPE-1 cells	Prostate	Homo sapiens (Human)	CVCL_3791
	22RV1 cells	Prostate	Homo sapiens (Human)	CVCL_1045
	VCaP cells	Prostate	Homo sapiens (Human)	CVCL_2235
	WPE1-NA22 cells	Prostate	Homo sapiens (Human)	CVCL_3810
	WPE1-NB11 cells	Prostate	Homo sapiens (Human)	CVCL_3811
	WPE1-NB14 cells	Prostate	Homo sapiens (Human)	CVCL_3812
	WPE1-NB26 cells	Prostate	Homo sapiens (Human)	CVCL_3813
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	miR-205 and miR-31 regulate apoptosis in prostate cancer cells by targeting antiapoptotic proteins Bcl-w and E2F6.
Key Molecule: Transcription factor E2F6 (E2F6)				[46]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell proliferation		Inhibition	hsa05200
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
	RWPE-1 cells	Prostate	Homo sapiens (Human)	CVCL_3791
	22RV1 cells	Prostate	Homo sapiens (Human)	CVCL_1045
	VCaP cells	Prostate	Homo sapiens (Human)	CVCL_2235
	WPE1-NA22 cells	Prostate	Homo sapiens (Human)	CVCL_3810
	WPE1-NB11 cells	Prostate	Homo sapiens (Human)	CVCL_3811
	WPE1-NB14 cells	Prostate	Homo sapiens (Human)	CVCL_3812
	WPE1-NB26 cells	Prostate	Homo sapiens (Human)	CVCL_3813
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	miR-205 and miR-31 regulate apoptosis in prostate cancer cells by targeting antiapoptotic proteins Bcl-w and E2F6.
Key Molecule: Programmed cell death protein 4 (PDCD4)				[52]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell proliferation		Activation	hsa05200
In Vitro Model	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	Programmed cell death 4 (PDCD4), is a novel suppressor of tumorigenesis, tumor progression and invasion. miR-21 can directly down-regulate the expression of PDCD4 by targeting its 3'UTR in PC3 cells. PDCD4, a direct target gene of miR-21, could mediate chemoresistance to docetaxel in PC3 cells.
Key Molecule: Cholinergic receptor muscarinic 1 (CHRM1)				[58]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	MAPK signaling pathway		Activation	hsa04010
In Vitro Model	22Rv1DTXR cells	Prostate	Homo sapiens (Human)	N.A.
	PC-3DTXR cells	Prostate	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Western blot assay
Experiment for Drug Resistance	Cell proliferation assay; Soft-agar colony formation assay; Tumorsphere formation assay
Mechanism Description	Here, we demonstrate activation of the cholinergic muscarinic M1 receptor (CHRM1) in CRPC cells upon acquiring resistance to docetaxel, which is manifested in tumor tissues from PC patients post- vs. pre-docetaxel. Genetic and pharmacological inactivation of CHRM1 restores the efficacy of docetaxel in resistant cells. Mechanistically, CHRM1, via its first and third extracellular loops, interacts with the SEMA domain of cMET and forms a heteroreceptor complex with cMET, stimulating a downstream mitogen-activated protein polykinase program to confer docetaxel resistance.
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: hsa-mir-323				[31]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay; Flow cytometric analysis
Mechanism Description	microRNA-323 upregulation promotes prostate cancer growth and docetaxel resistance by repressing p73.
Key Molecule: hsa-mir-181a				[48]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	C4-2B cells	Prostate	Homo sapiens (Human)	CVCL_4784
	TaxR cells	Prostate	Homo sapiens (Human)	CVCL_4V97
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	Beckman Coulter method; Rhodamine Assay; Cell Death ELISA
Mechanism Description	Overexpression of miR181a in prostate cancer cells contributes to their resistance to docetaxel, this is due, in part, to modulation of p53 phosphorylation and apoptosis.
Key Molecule: hsa-miR-125a-3p				[7]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	MTA1 signaling pathway		Activation	hsa05206
In Vitro Model	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	ELISA; MTT assay
Mechanism Description	Regulation of docetaxel sensitivity in prostate cancer cells by hsa-miR125a-3p via modulation of metastasis-associated protein 1 signaling, MTA1 is a direct target of hsa-mir125a-3p in pca cells.
Key Molecule: hsa-mir-375				[28]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	CCK8 assay; Annexin V-PE Apoptosis assay
Mechanism Description	miR375 induces docetaxel resistance in prostate cancer by targeting SEC23A and YAP1.
Key Molecule: hsa-mir-195				[49]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell colony		Activation	hsa05200
	Cell viability		Activation	hsa05200
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay
Mechanism Description	miR-195 improved the sensitivity of resistant PC cells to DOC by suppressing CLU.
Key Molecule: Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)				[17]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell invasion		Activation	hsa05200
	Cell proliferation		Activation	hsa05200
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qPCR
Experiment for Drug Resistance	MTT assay; Scratch Wound healing assay; Transwell Invasion assay; Flow cytometry assay
Mechanism Description	Knockdown of MALAT1 in DTX-resistant PCa cells up-regulated miR-145-5p as well as suppressed AkAP12 expression, further inhibited cell viability and induced apoptosis.
Key Molecule: SOCS2 antisense RNA 1 (SOCS2-AS1)				[21]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell proliferation		Activation	hsa05200
In Vitro Model	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
	VCaP cells	Prostate	Homo sapiens (Human)	CVCL_2235
	LTAD cells	Prostate	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	qPCR
Experiment for Drug Resistance	TUNEL assay; MTS assay
Mechanism Description	Androgen-induced Long Noncoding RNA (LncRNA) SOCS2-AS1 Promotes Cell Growth and Inhibits Apoptosis in Prostate Cancer Cells.suppressor of cytokine signaling 2-antisense transcript 1 (SOCS2-AS1), the expression of which was higher in castration-resistant prostate cancer model cells.SOCS2-AS1 promoted castration-resistant and androgen-dependent cell growth. We found that SOCS2-AS1 knockdown up-regulated genes related to the apoptosis pathway, including tumor necrosis factor superfamily 10 (TNFSF10), and sensitized prostate cancer cells to docetaxel treatment. Moreover, we also demonstrated that SOCS2-AS1 promotes androgen signaling by modulating the epigenetic control for AR target genes including TNFSF10 These findings suggest that SOCS2-AS1 plays an important role in the development of castration-resistant prostate cancer by repressing apoptosis.
Key Molecule: hsa-mir-34				[8]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell proliferation		Activation	hsa05200
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
	22RV1 cells	Prostate	Homo sapiens (Human)	CVCL_1045
Experiment for Molecule Alteration	qPCR
Experiment for Drug Resistance	Acid phosphatase assay
Mechanism Description	miR-34a regulates BCL-2 and may, in part, regulate response to docetaxel. miR-34a was significantly decreased in prostate cancer versus normal tissues; in biochemical recurrence versus non-recurrence tissue and in metastatic versus primary disease prostate tissue. We confirmed BCL-2 as a target of miR-34a, by manipulating miR-34a expression in our parent and docetaxel resistant cell lines and subsequently assessing BCL-2 levels. Specifically, upon inhibition of miR-34a in sensitive parent cells (PC3 and 22Rv1) we observed an increase in BCL-2 expression, whereas mimicking miR-34a expression in docetaxel-resistant cells (PC3RD and 22Rv1RD) resulted in decreased BCL-2 expression.
Key Molecule: hsa-mir-205				[46], [50]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell proliferation		Activation	hsa05200
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
	RWPE-1 cells	Prostate	Homo sapiens (Human)	CVCL_3791
	22RV1 cells	Prostate	Homo sapiens (Human)	CVCL_1045
	VCaP cells	Prostate	Homo sapiens (Human)	CVCL_2235
	WPE1-NA22 cells	Prostate	Homo sapiens (Human)	CVCL_3810
	WPE1-NB11 cells	Prostate	Homo sapiens (Human)	CVCL_3811
	WPE1-NB14 cells	Prostate	Homo sapiens (Human)	CVCL_3812
	WPE1-NB26 cells	Prostate	Homo sapiens (Human)	CVCL_3813
Experiment for Molecule Alteration	RT-qPCR
Experiment for Drug Resistance	MTT assay; Flow cytometry assay
Mechanism Description	Docetaxel-resistant cells showed a reduced E-cadherin and an increased vimentin expression accompanied by induced expression of stem cell markers compared with parental cells. Decreased Expression of miR-200c and miR-205 Is Responsible for E-Cadherin Loss in Chemotherapy-Resistant Cells. And miR-205 and miR-31 regulate apoptosis in prostate cancer cells by targeting antiapoptotic proteins Bcl-w and E2F6.
Key Molecule: Growth arrest specific 5 (GAS5)				[51]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
In Vitro Model	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
	22RV1 cells	Prostate	Homo sapiens (Human)	CVCL_1045
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	Fluorescence microscopy test apoptosis assay
Mechanism Description	Transient expression of GAS5 enhances apoptosis and decreases the survival of 22Rv1 cells, forced variation of GAS5 gene expression can modulate cellular responses to various apoptotic stimuli, including a range of chemotherapeutic drugs.
Key Molecule: hsa-mir-200c				[50]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
Experiment for Molecule Alteration	RT-qPCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	Docetaxel-resistant cells showed a reduced E-cadherin and an increased vimentin expression accompanied by induced expression of stem cell markers compared with parental cells. Decreased Expression of miR-200c and miR-205 Is Responsible for E-Cadherin Loss in Chemotherapy-Resistant Cells.
Key Molecule: hsa-mir-31				[46]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell proliferation		Inhibition	hsa05200
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
	RWPE-1 cells	Prostate	Homo sapiens (Human)	CVCL_3791
	22RV1 cells	Prostate	Homo sapiens (Human)	CVCL_1045
	VCaP cells	Prostate	Homo sapiens (Human)	CVCL_2235
	WPE1-NA22 cells	Prostate	Homo sapiens (Human)	CVCL_3810
	WPE1-NB11 cells	Prostate	Homo sapiens (Human)	CVCL_3811
	WPE1-NB14 cells	Prostate	Homo sapiens (Human)	CVCL_3812
	WPE1-NB26 cells	Prostate	Homo sapiens (Human)	CVCL_3813
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	miR-205 and miR-31 regulate apoptosis in prostate cancer cells by targeting antiapoptotic proteins Bcl-w and E2F6.
Key Molecule: hsa-mir-21				[52]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell proliferation		Activation	hsa05200
In Vitro Model	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	Programmed cell death 4 (PDCD4), is a novel suppressor of tumorigenesis, tumor progression and invasion. miR-21 can directly down-regulate the expression of PDCD4 by targeting its 3'UTR in PC3 cells. PDCD4, a direct target gene of miR-21, could mediate chemoresistance to docetaxel in PC3 cells.
Regulation by the Disease Microenvironment (RTDM)			Click to Show/Hide
Key Molecule: Angiopoietin-related protein 4 (ANGPTL4)				[57]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	22Rv-1 cells	Prostate	Homo sapiens (Human)	CVCL_1045
	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	Flow cytometric assay
Mechanism Description	This research demonstrated that ANGPTL4 is primarily expressed in CAFs and that ANGPTL4 can bind to IQGAP1 on the PCa cell membrane, activating the Raf-MEK-ERK-PGC1 pathway. This process promotes mitochondrial biogenesis and OXPHOS function, ultimately leading to growth and chemoresistance in PCa.
Key Molecule: Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A)				[57]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	22Rv-1 cells	Prostate	Homo sapiens (Human)	CVCL_1045
	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
Experiment for Molecule Alteration	Western blot assay; qRT-PCR
Experiment for Drug Resistance	Flow cytometric assay
Mechanism Description	This research demonstrated that ANGPTL4 is primarily expressed in CAFs and that ANGPTL4 can bind to IQGAP1 on the PCa cell membrane, activating the Raf-MEK-ERK-PGC1 pathway. This process promotes mitochondrial biogenesis and OXPHOS function, ultimately leading to growth and chemoresistance in PCa.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Forkhead box protein O3 (FOXO3)				[13]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]
Sensitive Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate cancer
The Studied Tissue	Prostate
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 2.55E-01 Fold-change: 1.97E-02 Z-score: 1.16E+00
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
Cell Pathway Regulation	Cell viability		Inhibition	hsa05200
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
	C4-2 cells	Prostate	Homo sapiens (Human)	CVCL_4782
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay; TUNEL assay; Flow cytometry assay
Mechanism Description	miR-223-3p inhibitor sensitized prostatic cancer mouse model to docetaxel by increasing the expression of FOXO3.
Key Molecule: Transcription regulator protein BACH2 (BACH2)				[59]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]
Sensitive Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	miR193a-5p/Bach2/HO1 signaling pathway		Inhibition	hsa05206
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
	T24 cells	Bladder	Homo sapiens (Human)	CVCL_0554
	RWPE-1 cells	Prostate	Homo sapiens (Human)	CVCL_3791
	UM-UC-3 cells	Bladder	Homo sapiens (Human)	CVCL_1783
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis; Luciferase reporter assay; Immunofluorescence staining assay
Experiment for Drug Resistance	TUNEL assays
Mechanism Description	Silencing of miR193a-5p or blockade of the miR193a-5p-Bach2-HO-1 pathway enhances sensitization of PC3 cells to docetaxel-induced apoptosis. Docetaxel-induced miR193a-5p upregulation, which in turn inhibits Bach2 expression and thus relieves Bach2 repression of HO-1 expression, partly counteracted docetaxel-induced apoptosis.
Key Molecule: NAD-dependent protein deacetylase sirtuin-1 (SIRT1)				[60]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]
Sensitive Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	UCA1/miR204/Sirt1 signaling pathway		Activation	hsa05206
In Vitro Model	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
	22RV1 cells	Prostate	Homo sapiens (Human)	CVCL_1045
	PNT2 cells	Prostate	Homo sapiens (Human)	CVCL_2164
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay; Annexin V-FITC Apoptosis assay; Flow cytometer
Mechanism Description	The UCA1/miR204/Sirt1 axis modulates docetaxel sensitivity of prostate cancer cells. miR204 negatively modulated Sirt1 expression in prostate cancer cells.
Key Molecule: Polycomb complex protein BMI-1 (BMI1)				[61]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]
Sensitive Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell migration		Inhibition	hsa04670
	Cell proliferation		Inhibition	hsa05200
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	Bmi-1 is expressed at a high level in PCa. miR-200b plays a pivotal role in PCa at least in part via downregulation of the oncogene Bmi-1, inhibition of Bmi-1 enhanced the antitumor activity of docetaxel in PCa cells.
Key Molecule: GTPase KRas (KRAS)				[62]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]
Sensitive Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell migration		Inhibition	hsa04670
	Cell proliferation		Inhibition	hsa05200
	EGFR/RAS/MAPK signaling pathway		Inhibition	hsa01521
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
In Vitro Model	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	miR-143 plays an important role in prostate cancer proliferation, migration and chemosensitivity by suppressing kRAS and subsequent inactivation of MAPk pathway.
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: Cancer susceptibility 2 (CASC2)				[20]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]
Sensitive Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate adenocarcinoma
The Studied Tissue	Prostate
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 4.71E-02 Fold-change: 1.02E-01 Z-score: 1.99E+00
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	ERK signaling pathway		Regulation	N.A.
Cell Pathway Regulation	RTK signaling pathway		Inhibition	hsa04015
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
	RWPE-1 cells	Prostate	Homo sapiens (Human)	CVCL_3791
	C4-2 cells	Prostate	Homo sapiens (Human)	CVCL_4782
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	MTT assay; Flow cytometer assay
Mechanism Description	CASC2 directly targets miR183 to inhibit its expression. SPRY2 is regarded as a negative regulator RTk signaling pathway, antagonizing cell migration and/or cellular differentiation occurring through the ERk signaling. CASC2 competes with SPRY2 for miR183 binding to rescue the expression of SPRY2 in PC cells, thus suppressing the cell proliferation and promoting the apoptosis of PC cells, finally enhancing PC cells chemo-sensitivity to docetaxel through SPRY2 downstream ERk signaling pathway.
Key Molecule: hsa-mir-183				[20]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]
Sensitive Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	ERK signaling pathway		Regulation	N.A.
Cell Pathway Regulation	RTK signaling pathway		Inhibition	hsa04015
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
	RWPE-1 cells	Prostate	Homo sapiens (Human)	CVCL_3791
	C4-2 cells	Prostate	Homo sapiens (Human)	CVCL_4782
Experiment for Molecule Alteration	Immunoblotting assay
Experiment for Drug Resistance	MTT assay; Flow cytometer assay
Mechanism Description	CASC2 directly targets miR183 to inhibit its expression. SPRY2 is regarded as a negative regulator RTk signaling pathway, antagonizing cell migration and/or cellular differentiation occurring through the ERk signaling. CASC2 competes with SPRY2 for miR183 binding to rescue the expression of SPRY2 in PC cells, thus suppressing the cell proliferation and promoting the apoptosis of PC cells, finally enhancing PC cells chemo-sensitivity to docetaxel through SPRY2 downstream ERk signaling pathway.
Key Molecule: Protein sprouty homolog 2 (SPRY2)				[20]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]
Sensitive Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	ERK signaling pathway		Regulation	N.A.
Cell Pathway Regulation	RTK signaling pathway		Inhibition	hsa04015
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
	RWPE-1 cells	Prostate	Homo sapiens (Human)	CVCL_3791
	C4-2 cells	Prostate	Homo sapiens (Human)	CVCL_4782
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	MTT assay; Flow cytometer assay
Mechanism Description	SPRY2 is a direct downstream target of miR183 and can be negatively regulated by miR183 and is regarded as a negative regulator RTk signaling pathway, antagonizing cell migration and/or cellular differentiation occurring through the ERk signaling. CASC2 competes with SPRY2 for miR183 binding to rescue the expression of SPRY2 in PC cells, thus suppressing the cell proliferation and promoting the apoptosis of PC cells, finally enhancing PC cells chemo-sensitivity to docetaxel through SPRY2 downstream ERk signaling pathway.
Key Molecule: hsa-miR-193a-5p				[59]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]
Sensitive Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	miR193a-5p/Bach2/HO1 signaling pathway		Inhibition	hsa05206
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
	T24 cells	Bladder	Homo sapiens (Human)	CVCL_0554
	RWPE-1 cells	Prostate	Homo sapiens (Human)	CVCL_3791
	UM-UC-3 cells	Bladder	Homo sapiens (Human)	CVCL_1783
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	TUNEL assays
Mechanism Description	Silencing of miR193a-5p or blockade of the miR193a-5p-Bach2-HO-1 pathway enhances sensitization of PC3 cells to docetaxel-induced apoptosis. Docetaxel-induced miR193a-5p upregulation, which in turn inhibits Bach2 expression and thus relieves Bach2 repression of HO-1 expression, partly counteracted docetaxel-induced apoptosis.
Key Molecule: hsa-mir-204				[60]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]
Sensitive Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	UCA1/miR204/Sirt1 signaling pathway		Activation	hsa05206
In Vitro Model	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
	22RV1 cells	Prostate	Homo sapiens (Human)	CVCL_1045
	PNT2 cells	Prostate	Homo sapiens (Human)	CVCL_2164
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	CCK8 assay; Annexin V-FITC Apoptosis assay; Flow cytometer
Mechanism Description	The UCA1/miR204/Sirt1 axis modulates docetaxel sensitivity of prostate cancer cells. UCA1 upregulation directly resulted in decreased miR204 expression.
Key Molecule: Urothelial cancer associated 1 (UCA1)				[60]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]
Sensitive Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	UCA1/miR204/Sirt1 signaling pathway		Activation	hsa05206
In Vitro Model	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
	22RV1 cells	Prostate	Homo sapiens (Human)	CVCL_1045
	PNT2 cells	Prostate	Homo sapiens (Human)	CVCL_2164
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	CCK8 assay; Annexin V-FITC Apoptosis assay; Flow cytometer
Mechanism Description	The UCA1/miR204/Sirt1 axis modulates docetaxel sensitivity of prostate cancer cells. UCA1 upregulation directly resulted in decreased miR204 expression.
Key Molecule: hsa-miR-223-3p				[13]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]
Sensitive Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
Cell Pathway Regulation	Cell viability		Inhibition	hsa05200
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
	C4-2 cells	Prostate	Homo sapiens (Human)	CVCL_4782
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay; TUNEL assay; Flow cytometry assay
Mechanism Description	miR-223-3p inhibitor sensitized prostatic cancer mouse model to docetaxel by increasing the expression of FOXO3.
Key Molecule: hsa-mir-200b				[61]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]
Sensitive Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell migration		Inhibition	hsa04670
	Cell proliferation		Inhibition	hsa05200
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	Bmi-1 is expressed at a high level in PCa. miR-200b plays a pivotal role in PCa at least in part via downregulation of the oncogene Bmi-1, inhibition of Bmi-1 enhanced the antitumor activity of docetaxel in PCa cells.
Key Molecule: hsa-mir-143				[62]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]
Sensitive Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell migration		Inhibition	hsa04670
	Cell proliferation		Inhibition	hsa05200
	EGFR/RAS/MAPK signaling pathway		Inhibition	hsa01521
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
In Vitro Model	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	miR-143 plays an important role in prostate cancer proliferation, migration and chemosensitivity by suppressing kRAS and subsequent inactivation of MAPk pathway.
Regulation by the Disease Microenvironment (RTDM)			Click to Show/Hide
Key Molecule: Zinc finger E-box-binding homeobox 1 (ZEB1)				[63], [64]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]
Sensitive Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell invasion		Inhibition	hsa05200
	Cell migration		Inhibition	hsa04670
	Cell viability		Inhibition	hsa05200
	ZEB1 signaling pathway		Inhibition	hsa05215
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
	PrEC cells	Prostate	Homo sapiens (Human)	CVCL_0061
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis; Luciferase reporter assay
Experiment for Drug Resistance	MTT assay; Flow cytometric analysis
Mechanism Description	miR27b and miR34a enhance docetaxel sensitivity of prostate cancer cells through inhibiting epithelial-to-mesenchymal transition by targeting ZEB1. And microRNA-204 modulates chemosensitivity and apoptosis of prostate cancer cells by targeting ZEB1. Suppression of ZEB1 could effectively improve miR204 deficiency-triggered chemoresistance in PC cells.
Key Molecule: hsa-mir-27b				[64]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]
Sensitive Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
	PrEC cells	Prostate	Homo sapiens (Human)	CVCL_0061
	HEK293 cells	Kidney	Homo sapiens (Human)	CVCL_0045
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	miR27b and miR34a enhance docetaxel sensitivity of prostate cancer cells through inhibiting epithelial-to-mesenchymal transition by targeting ZEB1.
Key Molecule: hsa-mir-34				[64]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]
Sensitive Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
	PrEC cells	Prostate	Homo sapiens (Human)	CVCL_0061
	HEK293 cells	Kidney	Homo sapiens (Human)	CVCL_0045
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	miR27b and miR34a enhance docetaxel sensitivity of prostate cancer cells through inhibiting epithelial-to-mesenchymal transition by targeting ZEB1.

Temsirolimus

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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: Growth arrest specific 5 (GAS5)				[5]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]
Sensitive Drug	Temsirolimus			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate adenocarcinoma
The Studied Tissue	Prostate
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 1.54E-18 Fold-change: 5.36E-01 Z-score: 9.11E+00
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell proliferation		Inhibition	hsa05200
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
	22RV1 cells	Prostate	Homo sapiens (Human)	CVCL_1045
	PNT2C2 cells	Prostate	Homo sapiens (Human)	CVCL_4889
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	GAS5 assay; MTS assay
Mechanism Description	First generation mTORC1, combined mTORC1/mTORC2 and dual PI3k/mTOR inhibitors all increased cellular GAS5 levels and inhibited culture growth in androgen-dependent (LNCaP) and androgen-sensitive (22Rv1) cell lines, but not in androgen-independent (PC-3 and DU 145) cell lines. The latter exhibited low endogenous GAS5 expression, and GAS5 silencing in LNCaP and 22Rv1 cells decreased the sensitivity to mTOR inhibitors, whereas transfection of GAS5 LncRNA sensitized PC-3 and DU 145 cells to these agents.

Olaparib

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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: Prostate cancer associated transcript 1 (PCAT1)				[9]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]
Sensitive Drug	Olaparib			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate adenocarcinoma
The Studied Tissue	Prostate
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 3.05E-25 Fold-change: 3.43E+00 Z-score: 1.10E+01
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
	RWPE cells	Prostate	Homo sapiens (Human)	CVCL_1736
In Vivo Model	SCID nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qPCR
Experiment for Drug Resistance	WST assay
Mechanism Description	PCAT-1 expressing cells exhibit a BRCA-like phenotype, resulting in cell sensitization to PARP1 inhibitors. In human prostate cancer tissues, high PCAT-1 expression predicts for low BRCA2 expression, supporting our observations in model systems.

Paclitaxel

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Tyrosine-protein kinase Yes (YES1)				[10]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Paclitaxel			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate cancer
The Studied Tissue	Prostate
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 8.64E-01 Fold-change: 3.34E-03 Z-score: 1.72E-01
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	PC3/TXR cells	Prostate	Homo sapiens (Human)	CVCL_0035
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis; Luciferase reporter assay
Experiment for Drug Resistance	MTT assay; Annexin V-FITC and PI Flow cytometry assay
Mechanism Description	Overexpression of miR199a inhibited PTX resistance. YES1 was a target of miR199a, and overexpression of YES1 reversed the effect of miR199a in suppressing PTX resistance. In vivo, miR199a increased tumor PTX sensitivity.
Key Molecule: SLAIN motif-containing protein 1 (SLAIN1)				[11]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Paclitaxel			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate cancer
The Studied Tissue	Prostate
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 4.28E-04 Fold-change: 3.25E-01 Z-score: 4.11E+00
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Caspase-3 signaling pathway		Activation	hsa04210
	Cell apoptosis		Inhibition	hsa04210
In Vitro Model	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CellTiter-Glo luminescent cell viability assay
Mechanism Description	Restoration of miR-130a activated caspase-8 and increased the drug sensitivity in taxane-resistant prostate cancer cells, suggesting that miR-130a may become a potential target for therapy of taxane-resistant CRPC. Since the mechanism of the action of miR-130a was different from that of paclitaxel, a combination therapy of paclitaxel and miR-130a mimic may be effective in treatment of CRPC. Furthermore, it was reported that miR-130a expression was decreased in prostate cancer tissues. It is therefore possible that the restoration of miR-130a could be an effective approach for treating not only taxane-resistant prostate cancer but also prostate cancer with reduced expression of miR-130a.
Key Molecule: Transcription factor GATA6 (GATA6)				[16]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Paclitaxel			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate cancer
The Studied Tissue	Prostate
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 2.12E-02 Fold-change: 1.34E-01 Z-score: 2.48E+00
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
	RWPE-1 cells	Prostate	Homo sapiens (Human)	CVCL_3791
Experiment for Molecule Alteration	Western blot analysis; RT-qPCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	Long non-coding RNA Linc00518 Can enhance GATA6 expression by suppressing miR-216b-5p expression to promotes paclitaxel resistance in the human prostate cancer.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Ribosomal protein S6 kinase alpha-5 (RPS6KA5)				[33]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]
Sensitive Drug	Paclitaxel			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate cancer
The Studied Tissue	Prostate
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 3.96E-07 Fold-change: -1.87E-01 Z-score: -5.71E+00
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell invasion		Inhibition	hsa05200
	Cell migration		Inhibition	hsa04670
	Cell proliferation		Inhibition	hsa05200
	MSK1 signaling pathway		Inhibition	hsa04010
In Vitro Model	PC3PR cells	Prostate	Homo sapiens (Human)	CVCL_0035
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Cell Growth Assay
Mechanism Description	MSk1 is a novel target gene of miR-148a in both PC3 and PC3PR cells and miR-148 attenuates paclitaxel-resistance of PC3PR cells by modulating MSk1 expression.

Cabazitaxel

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Tubulin beta-3 chain (TUBB3)				[12]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Cabazitaxel			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate cancer
The Studied Tissue	Prostate
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 2.82E-01 Fold-change: 2.20E-02 Z-score: 1.10E+00
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	CAL27 cells	Oral	Homo sapiens (Human)	CVCL_1107
	LOVO cells	Colon	Homo sapiens (Human)	CVCL_0399
	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	C4-2 cells	Prostate	Homo sapiens (Human)	CVCL_4782
	HuTu80 cells	Small intestine	Homo sapiens (Human)	CVCL_1301
	DU145-DR cells	Brain	Homo sapiens (Human)	CVCL_4Y36
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	TUBB3 expression was upregulated in DTX-resistant and CBZ-resistant cells. TUBB3 knockdown re-sensitized DTX-resistant cells to DTX and CBZ-resistant cells to CBZ. Additionally, TUBB3 knockdown re-sensitized DTX-resistant cell lines to CBZ, indicating that TUBB3 mediates cross-resistance between DTX and CBZ. Knockdown of TUBB3 enhanced PTEN expression, and PTEN knockout enhanced TUBB3 expression.
Key Molecule: Phosphatase and tensin homolog (PTEN)				[12]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Cabazitaxel			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	CAL27 cells	Oral	Homo sapiens (Human)	CVCL_1107
	LOVO cells	Colon	Homo sapiens (Human)	CVCL_0399
	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	C4-2 cells	Prostate	Homo sapiens (Human)	CVCL_4782
	HuTu80 cells	Small intestine	Homo sapiens (Human)	CVCL_1301
	DU145-DR cells	Brain	Homo sapiens (Human)	CVCL_4Y36
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	TUBB3 expression was upregulated in DTX-resistant and CBZ-resistant cells. TUBB3 knockdown re-sensitized DTX-resistant cells to DTX and CBZ-resistant cells to CBZ. Additionally, TUBB3 knockdown re-sensitized DTX-resistant cell lines to CBZ, indicating that TUBB3 mediates cross-resistance between DTX and CBZ. Knockdown of TUBB3 enhanced PTEN expression, and PTEN knockout enhanced TUBB3 expression.
Key Molecule: Mitogen-activated protein kinase 1 (MAPK1)				[44]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Cabazitaxel			Drug Info
Molecule Alteration	Phosphorylation		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Oxytocin signaling pathway		Activation	hsa04921
In Vitro Model	DU145CR cells	prostate	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	MS analysis
Mechanism Description	Pathway analysis revealed that clusters in two cases showed up-regulation of the oxytocin (OXT) receptor-signaling pathway. Spatial gene expression analysis of CBZ-resistant prostate cancer tissues confirmed the heterogeneous expression of OXT-signaling molecules. We identified the OXT-signaling pathway as a potential target for CBZ-resistant CRPC using single-cell transcriptomic analysis of CTCs. CLO may potentially overcome CBZ resistance in CRPC by inhibiting the OXT-signaling pathway.
Key Molecule: Calcium/calmodulin-dependent protein kinase type II delta/gamma (CAMK2D/G)				[44]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Cabazitaxel			Drug Info
Molecule Alteration	Phosphorylation		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Oxytocin signaling pathway		Activation	hsa04921
In Vitro Model	DU145CR cells	prostate	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	MS analysis
Mechanism Description	Pathway analysis revealed that clusters in two cases showed up-regulation of the oxytocin (OXT) receptor-signaling pathway. Spatial gene expression analysis of CBZ-resistant prostate cancer tissues confirmed the heterogeneous expression of OXT-signaling molecules. We identified the OXT-signaling pathway as a potential target for CBZ-resistant CRPC using single-cell transcriptomic analysis of CTCs. CLO may potentially overcome CBZ resistance in CRPC by inhibiting the OXT-signaling pathway.
Key Molecule: Eukaryotic elongation factor 2 kinase (eEF2K)				[44]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Cabazitaxel			Drug Info
Molecule Alteration	Phosphorylation		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Oxytocin signaling pathway		Activation	hsa04921
In Vitro Model	DU145CR cells	prostate	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	MS analysis
Mechanism Description	Pathway analysis revealed that clusters in two cases showed up-regulation of the oxytocin (OXT) receptor-signaling pathway. Spatial gene expression analysis of CBZ-resistant prostate cancer tissues confirmed the heterogeneous expression of OXT-signaling molecules. We identified the OXT-signaling pathway as a potential target for CBZ-resistant CRPC using single-cell transcriptomic analysis of CTCs. CLO may potentially overcome CBZ resistance in CRPC by inhibiting the OXT-signaling pathway.
Key Molecule: Guanine nucleotide-binding protein G(i) subunit alpha-2 (GNAI2)				[44]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Cabazitaxel			Drug Info
Molecule Alteration	Phosphorylation		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Oxytocin signaling pathway		Activation	hsa04921
In Vitro Model	DU145CR cells	prostate	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	MS analysis
Mechanism Description	Pathway analysis revealed that clusters in two cases showed up-regulation of the oxytocin (OXT) receptor-signaling pathway. Spatial gene expression analysis of CBZ-resistant prostate cancer tissues confirmed the heterogeneous expression of OXT-signaling molecules. We identified the OXT-signaling pathway as a potential target for CBZ-resistant CRPC using single-cell transcriptomic analysis of CTCs. CLO may potentially overcome CBZ resistance in CRPC by inhibiting the OXT-signaling pathway.
Key Molecule: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 (PLCB3)				[44]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Cabazitaxel			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Cell Pathway Regulation	Oxytocin signaling pathway		Activation	hsa04921
Experiment for Molecule Alteration	Gene expression analysis
Mechanism Description	Pathway analysis revealed that clusters in two cases showed up-regulation of the oxytocin (OXT) receptor-signaling pathway. Spatial gene expression analysis of CBZ-resistant prostate cancer tissues confirmed the heterogeneous expression of OXT-signaling molecules. We identified the OXT-signaling pathway as a potential target for CBZ-resistant CRPC using single-cell transcriptomic analysis of CTCs. CLO may potentially overcome CBZ resistance in CRPC by inhibiting the OXT-signaling pathway.
Key Molecule: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 (PLCB3)				[44]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Cabazitaxel			Drug Info
Molecule Alteration	Phosphorylation		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Oxytocin signaling pathway		Activation	hsa04921
In Vitro Model	DU145CR cells	prostate	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	MS analysis
Mechanism Description	Pathway analysis revealed that clusters in two cases showed up-regulation of the oxytocin (OXT) receptor-signaling pathway. Spatial gene expression analysis of CBZ-resistant prostate cancer tissues confirmed the heterogeneous expression of OXT-signaling molecules. We identified the OXT-signaling pathway as a potential target for CBZ-resistant CRPC using single-cell transcriptomic analysis of CTCs. CLO may potentially overcome CBZ resistance in CRPC by inhibiting the OXT-signaling pathway.
Key Molecule: 5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1)				[44]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Cabazitaxel			Drug Info
Molecule Alteration	Phosphorylation		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Oxytocin signaling pathway		Activation	hsa04921
In Vitro Model	DU145CR cells	prostate	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	MS analysis
Mechanism Description	Pathway analysis revealed that clusters in two cases showed up-regulation of the oxytocin (OXT) receptor-signaling pathway. Spatial gene expression analysis of CBZ-resistant prostate cancer tissues confirmed the heterogeneous expression of OXT-signaling molecules. We identified the OXT-signaling pathway as a potential target for CBZ-resistant CRPC using single-cell transcriptomic analysis of CTCs. CLO may potentially overcome CBZ resistance in CRPC by inhibiting the OXT-signaling pathway.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Phosphatase and tensin homolog (PTEN)				[12]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]
Sensitive Drug	Cabazitaxel			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate cancer
The Studied Tissue	Prostate
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 2.27E-02 Fold-change: 1.09E-01 Z-score: 2.44E+00
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	CAL27 cells	Oral	Homo sapiens (Human)	CVCL_1107
	LOVO cells	Colon	Homo sapiens (Human)	CVCL_0399
	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	C4-2 cells	Prostate	Homo sapiens (Human)	CVCL_4782
	HuTu80 cells	Small intestine	Homo sapiens (Human)	CVCL_1301
	DU145-DR cells	Brain	Homo sapiens (Human)	CVCL_4Y36
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	TUBB3 expression was upregulated in DTX-resistant and CBZ-resistant cells. TUBB3 knockdown re-sensitized DTX-resistant cells to DTX and CBZ-resistant cells to CBZ. Additionally, TUBB3 knockdown re-sensitized DTX-resistant cell lines to CBZ, indicating that TUBB3 mediates cross-resistance between DTX and CBZ. Knockdown of TUBB3 enhanced PTEN expression, and PTEN knockout enhanced TUBB3 expression.
Key Molecule: Tubulin beta-3 chain (TUBB3)				[12]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]
Sensitive Drug	Cabazitaxel			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	CAL27 cells	Oral	Homo sapiens (Human)	CVCL_1107
	LOVO cells	Colon	Homo sapiens (Human)	CVCL_0399
	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	C4-2 cells	Prostate	Homo sapiens (Human)	CVCL_4782
	HuTu80 cells	Small intestine	Homo sapiens (Human)	CVCL_1301
	DU145-DR cells	Brain	Homo sapiens (Human)	CVCL_4Y36
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	TUBB3 expression was upregulated in DTX-resistant and CBZ-resistant cells. TUBB3 knockdown re-sensitized DTX-resistant cells to DTX and CBZ-resistant cells to CBZ. Additionally, TUBB3 knockdown re-sensitized DTX-resistant cell lines to CBZ, indicating that TUBB3 mediates cross-resistance between DTX and CBZ. Knockdown of TUBB3 enhanced PTEN expression, and PTEN knockout enhanced TUBB3 expression.

Cisplatin

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Ectonucleoside triphosphate diphosphohydrolase 5 (ENTPD5)				[14]
Resistant Disease	Prostatic intraepithelial neoplasia [ICD-11: 2C82.2]
Resistant Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate cancer
The Studied Tissue	Prostate
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 1.95E-06 Fold-change: 1.89E-01 Z-score: 5.92E+00
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
In Vitro Model	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
In Vitro Model	PC-3 cells	Bone	Homo sapiens (Human)	CVCL_0035
Experiment for Molecule Alteration	qRT-PCR; Western blotting assay
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	Forced expression of the PCPH protein or, in particular, of the mt-PCPH oncoprotein increased the levels of phosphorylated PKCalpha concurrently with those of Ser70-phosphorylated and total Bcl-2 protein, thus promoting cisplatin resistance.
Key Molecule: BH3-interacting domain death agonist (BID)				[22]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate cancer
The Studied Tissue	Prostate
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 8.58E-01 Fold-change: -7.54E-03 Z-score: -1.81E-01
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	AKT/ERK signaling pathway		Activation	hsa04010
	Cell apoptosis		Inhibition	hsa04210
	Cell invasion		Activation	hsa05200
	Cell migration		Activation	hsa04670
	Cell proliferation		Activation	hsa05200
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	miR-17-92 cluster plays a crucial role in cell growth of the DU145 prostate cancer cells due to regulation of cellular apoptosis-related and proliferation-related proteins, and causes chemo-resistance to cisplatin via activating AkT signaling together with upregulating ERCC1 also contributed to development of cisplatin-resistance.
Key Molecule: Bcl-2-associated agonist of cell death (BAD)				[22]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate cancer
The Studied Tissue	Prostate
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 3.50E-03 Fold-change: -9.12E-02 Z-score: -3.18E+00
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	AKT/ERK signaling pathway		Activation	hsa04010
	Cell apoptosis		Inhibition	hsa04210
	Cell invasion		Activation	hsa05200
	Cell migration		Activation	hsa04670
	Cell proliferation		Activation	hsa05200
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	miR-17-92 cluster plays a crucial role in cell growth of the DU145 prostate cancer cells due to regulation of cellular apoptosis-related and proliferation-related proteins, and causes chemo-resistance to cisplatin via activating AkT signaling together with upregulating ERCC1 also contributed to development of cisplatin-resistance.
Key Molecule: Bcl-2-like protein 11 (BCL2L11)				[22]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate cancer
The Studied Tissue	Prostate
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 4.20E-04 Fold-change: -1.26E-01 Z-score: -3.89E+00
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	AKT/ERK signaling pathway		Activation	hsa04010
	Cell apoptosis		Inhibition	hsa04210
	Cell invasion		Activation	hsa05200
	Cell migration		Activation	hsa04670
	Cell proliferation		Activation	hsa05200
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
In Vivo Model	BALB/c nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	miR-17-92 cluster plays a crucial role in cell growth of the DU145 prostate cancer cells due to regulation of cellular apoptosis-related and proliferation-related proteins, and causes chemo-resistance to cisplatin via activating AkT signaling together with upregulating ERCC1 also contributed to development of cisplatin-resistance.
Key Molecule: Branched-chain-amino-acid aminotransferase (BCAT1)				[45]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell invasion		Activation	hsa05200
	Cell migration		Activation	hsa04670
	Cell viability		Activation	hsa05200
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
In Vitro Model	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay; Flow cytometric analysis
Mechanism Description	Overexpression of miR218 inhibited cell viability, migration, and invasion in PC3 and DU145 cells. Overexpression of BCAT1 decreased the chemosensitivity to CDDP treatment of PC3 and DU145 cells. The tumor suppressive role of miR218 was mediated by negatively regulating BCAT1 protein expression.
Key Molecule: Bcl-2-interacting killer (BIK)				[22]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	AKT/ERK signaling pathway		Activation	hsa04010
	Cell apoptosis		Inhibition	hsa04210
	Cell invasion		Activation	hsa05200
	Cell migration		Activation	hsa04670
	Cell proliferation		Activation	hsa05200
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	miR-17-92 cluster plays a crucial role in cell growth of the DU145 prostate cancer cells due to regulation of cellular apoptosis-related and proliferation-related proteins, and causes chemo-resistance to cisplatin via activating AkT signaling together with upregulating ERCC1 also contributed to development of cisplatin-resistance.
Key Molecule: Bcl-2-like protein 2 (BCL2L2)				[46]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell proliferation		Inhibition	hsa05200
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
	RWPE-1 cells	Prostate	Homo sapiens (Human)	CVCL_3791
	22RV1 cells	Prostate	Homo sapiens (Human)	CVCL_1045
	VCaP cells	Prostate	Homo sapiens (Human)	CVCL_2235
	WPE1-NA22 cells	Prostate	Homo sapiens (Human)	CVCL_3810
	WPE1-NB11 cells	Prostate	Homo sapiens (Human)	CVCL_3811
	WPE1-NB14 cells	Prostate	Homo sapiens (Human)	CVCL_3812
	WPE1-NB26 cells	Prostate	Homo sapiens (Human)	CVCL_3813
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	miR-205 and miR-31 regulate apoptosis in prostate cancer cells by targeting antiapoptotic proteins Bcl-w and E2F6.
Key Molecule: Transcription factor E2F6 (E2F6)				[46]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell proliferation		Inhibition	hsa05200
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
	RWPE-1 cells	Prostate	Homo sapiens (Human)	CVCL_3791
	22RV1 cells	Prostate	Homo sapiens (Human)	CVCL_1045
	VCaP cells	Prostate	Homo sapiens (Human)	CVCL_2235
	WPE1-NA22 cells	Prostate	Homo sapiens (Human)	CVCL_3810
	WPE1-NB11 cells	Prostate	Homo sapiens (Human)	CVCL_3811
	WPE1-NB14 cells	Prostate	Homo sapiens (Human)	CVCL_3812
	WPE1-NB26 cells	Prostate	Homo sapiens (Human)	CVCL_3813
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	miR-205 and miR-31 regulate apoptosis in prostate cancer cells by targeting antiapoptotic proteins Bcl-w and E2F6.
Key Molecule: G1/S-specific cyclin-D1 (CCND1)				[47]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
	22RV1 cells	Prostate	Homo sapiens (Human)	CVCL_1045
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	ATP cell viability assay
Mechanism Description	CCND1 may induce cisplatin resistance both through cell cycle control and inhibition of cellular apoptosis pathways, which have been previously observed37 and supported by our CCND1 knockdown study. The role of CCND1 in cell cycle control is well documented. CCND1 accumulates in cells at middle and late G1 phase and stimulate G1 progression to S phase. The proportion of parental cells in G1/0 correlated with the cisplatin sensitivity, with 833K cells having the highest G1/0 population cells and lowest EC50 value and GCT27 the lowest G1/0 population but highest EC50 score.
Key Molecule: Bcl-2-associated agonist of cell death (BAD)				[14]
Resistant Disease	Prostatic intraepithelial neoplasia [ICD-11: 2C82.2]
Resistant Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
In Vitro Model	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
In Vitro Model	PC-3 cells	Bone	Homo sapiens (Human)	CVCL_0035
Experiment for Molecule Alteration	qRT-PCR; Western blotting assay
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	Forced expression of the PCPH protein or, in particular, of the mt-PCPH oncoprotein increased the levels of phosphorylated PKCalpha concurrently with those of Ser70-phosphorylated and total Bcl-2 protein, thus promoting cisplatin resistance.
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: hsa-mir-218				[45]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell invasion		Activation	hsa05200
	Cell migration		Activation	hsa04670
	Cell viability		Activation	hsa05200
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
In Vitro Model	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
Experiment for Molecule Alteration	PCR
Experiment for Drug Resistance	CCK8 assay; Flow cytometric analysis
Mechanism Description	Overexpression of miR218 inhibited cell viability, migration, and invasion in PC3 and DU145 cells. Overexpression of BCAT1 decreased the chemosensitivity to CDDP treatment of PC3 and DU145 cells. The tumor suppressive role of miR218 was mediated by negatively regulating BCAT1 protein expression.
Key Molecule: hsa-miR-17-92				[22]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	AKT/ERK signaling pathway		Activation	hsa04010
	Cell apoptosis		Inhibition	hsa04210
	Cell invasion		Activation	hsa05200
	Cell migration		Activation	hsa04670
	Cell proliferation		Activation	hsa05200
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	miR-17-92 cluster plays a crucial role in cell growth of the DU145 prostate cancer cells due to regulation of cellular apoptosis-related and proliferation-related proteins, and causes chemo-resistance to cisplatin via activating AkT signaling together with upregulating ERCC1 also contributed to development of cisplatin-resistance.
Key Molecule: hsa-mir-205				[46]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell proliferation		Inhibition	hsa05200
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
	RWPE-1 cells	Prostate	Homo sapiens (Human)	CVCL_3791
	22RV1 cells	Prostate	Homo sapiens (Human)	CVCL_1045
	VCaP cells	Prostate	Homo sapiens (Human)	CVCL_2235
	WPE1-NA22 cells	Prostate	Homo sapiens (Human)	CVCL_3810
	WPE1-NB11 cells	Prostate	Homo sapiens (Human)	CVCL_3811
	WPE1-NB14 cells	Prostate	Homo sapiens (Human)	CVCL_3812
	WPE1-NB26 cells	Prostate	Homo sapiens (Human)	CVCL_3813
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	miR-205 and miR-31 regulate apoptosis in prostate cancer cells by targeting antiapoptotic proteins Bcl-w and E2F6.
Key Molecule: hsa-mir-31				[46]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell proliferation		Inhibition	hsa05200
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
	RWPE-1 cells	Prostate	Homo sapiens (Human)	CVCL_3791
	22RV1 cells	Prostate	Homo sapiens (Human)	CVCL_1045
	VCaP cells	Prostate	Homo sapiens (Human)	CVCL_2235
	WPE1-NA22 cells	Prostate	Homo sapiens (Human)	CVCL_3810
	WPE1-NB11 cells	Prostate	Homo sapiens (Human)	CVCL_3811
	WPE1-NB14 cells	Prostate	Homo sapiens (Human)	CVCL_3812
	WPE1-NB26 cells	Prostate	Homo sapiens (Human)	CVCL_3813
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	miR-205 and miR-31 regulate apoptosis in prostate cancer cells by targeting antiapoptotic proteins Bcl-w and E2F6.
Irregularity in Drug Uptake and Drug Efflux (IDUE)			Click to Show/Hide
Key Molecule: ATP-binding cassette sub-family C2 (ABCC2)				[19]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
In Vitro Model	22RV1 cells	Prostate	Homo sapiens (Human)	CVCL_1045
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	However, higher concentrations of probenecid (500 uM) failed to demonstrate a chemosensitizing effect. Consistent with this lower chemosensitizing efficacy in higher-concentration probenecid treatment, we observed that the expression of ABCG2, a drug-efflux transporter, increased in a dose-dependent manner following probenecid treatment. Thus, probenecid could enhance the chemosensitivity of 3D-cultured prostate cancer cells, but not at higher concentr.
Key Molecule: Multidrug resistance-associated protein 1 (MRP1)				[19]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
In Vitro Model	22RV1 cells	Prostate	Homo sapiens (Human)	CVCL_1045
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	However, higher concentrations of probenecid (500 uM) failed to demonstrate a chemosensitizing effect. Consistent with this lower chemosensitizing efficacy in higher-concentration probenecid treatment, we observed that the expression of ABCG2, a drug-efflux transporter, increased in a dose-dependent manner following probenecid treatment. Thus, probenecid could enhance the chemosensitivity of 3D-cultured prostate cancer cells, but not at higher concentr.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Regulation by the Disease Microenvironment (RTDM)			Click to Show/Hide
Key Molecule: Matrix metalloproteinase-9 (MMP9)				[24]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]
Sensitive Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate cancer
The Studied Tissue	Prostate
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 6.62E-01 Fold-change: -2.74E-02 Z-score: -4.42E-01
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell invasion		Inhibition	hsa05200
	Cell migration		Inhibition	hsa04670
	Cell viability		Inhibition	hsa05200
	ERK signaling pathway		Inhibition	hsa04210
	Epithelial mesenchymal transition signaling pathway		Inhibition	hsa01521
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
	VCaP cells	Prostate	Homo sapiens (Human)	CVCL_2235
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay
Mechanism Description	UTMD mediated miR 205 transfection increased the expression of caspase 9, cleaved caspase 9, cytochrome c and E cadherin, and decreased the expression of MMP 9 and p ERk,inhibiting PCa cell proliferation, migration and invasion, and promoted apoptosis modulated by cisplatin.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Lysosome-associated membrane glycoprotein 3 (LAMP3)				[25]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]
Sensitive Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate cancer
The Studied Tissue	Prostate
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 6.24E-01 Fold-change: -3.15E-02 Z-score: -4.95E-01
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
In Vivo Model	SCID nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Immunoblotting analysis
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	Lysosome disturbance caused by miR-205-mediated down-regulation of RAB27A and LAMP3 constraints the completion of the autophagic flux by compromising the maturation step and, consequently, interferes with the detoxifying capabilities by which PCa cells may become resistant to CDDP.
Key Molecule: Zinc finger E-box-binding homeobox 1 (ZEB1)				[32]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]
Sensitive Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate cancer
The Studied Tissue	Prostate
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 1.99E-03 Fold-change: -1.37E-01 Z-score: -3.47E+00
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell invasion		Inhibition	hsa05200
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
	HEK293T cells	Kidney	Homo sapiens (Human)	CVCL_0063
Experiment for Molecule Alteration	RT-PCR; Western blot analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	miR-128 binded to the 3'UTR of ZEB1 and inhibited its expression. And ZEB1 (+) PCa chemoresistance and invasion, while miR-128 could reverse that by down-regulated ZEB1. These indicated that miR-128-mediated sensitizing chemoresistance and inhibiting invasion of PCa cells by directly targeting ZEB1.
Key Molecule: Ras-related protein Rab-27A (RAP27A)				[25]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]
Sensitive Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
In Vivo Model	SCID nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Immunoblotting analysis
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	Lysosome disturbance caused by miR-205-mediated down-regulation of RAB27A and LAMP3 constraints the completion of the autophagic flux by compromising the maturation step and, consequently, interferes with the detoxifying capabilities by which PCa cells may become resistant to CDDP.
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: hsa-mir-205				[24]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]
Sensitive Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell invasion		Inhibition	hsa05200
	Cell migration		Inhibition	hsa04670
	Cell viability		Inhibition	hsa05200
	ERK signaling pathway		Inhibition	hsa04210
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
	VCaP cells	Prostate	Homo sapiens (Human)	CVCL_2235
Experiment for Molecule Alteration	RT-qPCR
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay
Mechanism Description	UTMD mediated miR 205 transfection increased the expression of caspase 9, cleaved caspase 9, cytochrome c and E cadherin, and decreased the expression of MMP 9 and p ERk,inhibiting PCa cell proliferation, migration and invasion, and promoted apoptosis modulated by cisplatin.
Key Molecule: hsa-mir-128a				[32]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]
Sensitive Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell invasion		Inhibition	hsa05200
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
	HEK293T cells	Kidney	Homo sapiens (Human)	CVCL_0063
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	miR-128 binded to the 3'UTR of ZEB1 and inhibited its expression. And ZEB1 (+) PCa chemoresistance and invasion, while miR-128 could reverse that by down-regulated ZEB1. These indicated that miR-128-mediated sensitizing chemoresistance and inhibiting invasion of PCa cells by directly targeting ZEB1.
Key Molecule: hsa-mir-205				[25]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]
Sensitive Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
In Vivo Model	SCID nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	Lysosome disturbance caused by miR-205-mediated down-regulation of RAB27A and LAMP3 constraints the completion of the autophagic flux by compromising the maturation step and, consequently, interferes with the detoxifying capabilities by which PCa cells may become resistant to CDDP.

Sulforaphane

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: Core histone macro-H2A.1 (H2AFY)				[26]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Sulforaphane			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate cancer
The Studied Tissue	Prostate
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 2.25E-01 Fold-change: -3.58E-02 Z-score: -1.24E+00
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell proliferation		Activation	hsa05200
In Vitro Model	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
Experiment for Molecule Alteration	qPCR
Experiment for Drug Resistance	Cell proliferation assay
Mechanism Description	Knockdown of LINC01116 with siRNA decreased proliferation of prostate cancer cells, and significantly upregulated several genes including GAPDH (regulates glycolysis), MAP1LC3B2 (autophagy) and H2AFY (chromatin structure) and LncRNA LINC01116 is upregulated in a human prostate cancer cell line, is decreased by SFN treatment, and promotes cell proliferation in a human cancer cell line.
Key Molecule: Glyceraldehyde-3-phosphate dehydrogenase 1 (GAPDH)				[26]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Sulforaphane			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate cancer
The Studied Tissue	Prostate
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 2.35E-05 Fold-change: -5.47E-02 Z-score: -4.95E+00
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell proliferation		Activation	hsa05200
In Vitro Model	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
Experiment for Molecule Alteration	qPCR
Experiment for Drug Resistance	Cell proliferation assay
Mechanism Description	Knockdown of LINC01116 with siRNA decreased proliferation of prostate cancer cells, and significantly upregulated several genes including GAPDH (regulates glycolysis), MAP1LC3B2 (autophagy) and H2AFY (chromatin structure) and LncRNA LINC01116 is upregulated in a human prostate cancer cell line, is decreased by SFN treatment, and promotes cell proliferation in a human cancer cell line.

Verteporfin

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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Transcriptional coactivator YAP1 (YAP1)				[29]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]
Sensitive Drug	Verteporfin			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate cancer
The Studied Tissue	Prostate
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 7.45E-03 Fold-change: -4.71E-02 Z-score: -2.78E+00
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	HEp-2 cells	Skin	Homo sapiens (Human)	CVCL_1906
	U251 cells	Brain	Homo sapiens (Human)	CVCL_0021
	BT474 cells	Breast	Homo sapiens (Human)	CVCL_0179
	A172 cells	Brain	Homo sapiens (Human)	CVCL_0131
	U87 cells	Brain	Homo sapiens (Human)	CVCL_0022
	H1299 cells	Lung	Homo sapiens (Human)	CVCL_0060
	Calu-3 cells	Lung	Homo sapiens (Human)	CVCL_0609
	HuTu80 cells	Small intestine	Homo sapiens (Human)	CVCL_1301
In Vivo Model	Male BALB/c nude mouse model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis; qRT-PCR
Experiment for Drug Resistance	WST-1 assay; Colony formation assay; Annexin V-FITC/PI Apoptosis assay
Mechanism Description	MYBL2 expression was significantly upregulated in CRPC tissues and cell lines. Overexpression of MYBL2 could facilitate castration-resistant growth and metastatic capacity in androgen-dependent PCa cells by promoting YAP1 transcriptional activity via modulating the activity of the Rho GTPases RhoA and LATS1 kinase. Importantly, targeting MYBL2, or treatment with either the YAP/TAZ inhibitor Verteporfin or the RhoA inhibitor Simvastatin, reversed the resistance to ADT and blocked bone metastasis in CRPC cells.
Key Molecule: Myb-related protein B (MYBL2)				[29]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]
Sensitive Drug	Verteporfin			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate cancer
The Studied Tissue	Prostate
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 3.51E-02 Fold-change: -9.80E-02 Z-score: -2.22E+00
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	HEp-2 cells	Skin	Homo sapiens (Human)	CVCL_1906
	U251 cells	Brain	Homo sapiens (Human)	CVCL_0021
	BT474 cells	Breast	Homo sapiens (Human)	CVCL_0179
	A172 cells	Brain	Homo sapiens (Human)	CVCL_0131
	U87 cells	Brain	Homo sapiens (Human)	CVCL_0022
	H1299 cells	Lung	Homo sapiens (Human)	CVCL_0060
	Calu-3 cells	Lung	Homo sapiens (Human)	CVCL_0609
	HuTu80 cells	Small intestine	Homo sapiens (Human)	CVCL_1301
In Vivo Model	Male BALB/c nude mouse model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis; qRT-PCR
Experiment for Drug Resistance	WST-1 assay; Colony formation assay; Annexin V-FITC/PI Apoptosis assay
Mechanism Description	MYBL2 expression was significantly upregulated in CRPC tissues and cell lines. Overexpression of MYBL2 could facilitate castration-resistant growth and metastatic capacity in androgen-dependent PCa cells by promoting YAP1 transcriptional activity via modulating the activity of the Rho GTPases RhoA and LATS1 kinase. Importantly, targeting MYBL2, or treatment with either the YAP/TAZ inhibitor Verteporfin or the RhoA inhibitor Simvastatin, reversed the resistance to ADT and blocked bone metastasis in CRPC cells.

Abiraterone

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)		Click to Show/Hide
Key Molecule: Androgen receptor (AR)			[39]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Abiraterone		Drug Info
Molecule Alteration	Structural variation	Copy number gain	Molecule Info
Experimental Note	Identified from the Human Clinical Data
Experiment for Molecule Alteration	Whole genome sequencing assay; Exome sequencing assay
Mechanism Description	Accordingly, AR amplification was detected in circulating cell-free DNA and was shown to be associated with enzalutamide and abiraterone treatment resistance in a cohort of 62 CRPC patients.
Key Molecule: Androgen receptor (AR)			[39]
Resistant Disease	Primary prostate cancer [ICD-11: 2C82.Z]
Resistant Drug	Abiraterone		Drug Info
Molecule Alteration	Structural variation	Copy number gain	Molecule Info
Experimental Note	Identified from the Human Clinical Data
Experiment for Molecule Alteration	Whole genome sequencing assay; Exome sequencing assay
Mechanism Description	Accordingly, AR amplification was detected in circulating cell-free DNA and was shown to be associated with enzalutamide and abiraterone treatment resistance in a cohort of 62 CRPC patients.

Apalutamide

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Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

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Key Molecule: Androgen receptor (AR)

[40]

Resistant Disease

Prostate cancer [ICD-11: 2C82.0]

Resistant Drug

Apalutamide

Drug Info

Molecule Alteration

Missense mutation

p.F877L (c.2629T>C)

Molecule Info

Wild Type Structure

Method: X-ray diffraction

Resolution: 1.44 Å

PDB: 5V8Q

Mutant Type Structure

Method: X-ray diffraction

Resolution: 1.69 Å

PDB: 8FH1

Download The Information of Sequence

Download The Structure File

Click to Show/Hide the Structure

Experimental Note

Revealed Based on the Cell Line Data

In Vitro Model

LNCaP cells

Prostate

Homo sapiens (Human)

CVCL_0395

PC3 cells

Prostate

Homo sapiens (Human)

CVCL_0035

In Vivo Model

SHO male mouse xenograft model

Mus musculus

Experiment for
Molecule Alteration

Chromatin immunoprecipitation assay

Mechanism Description

The missense mutation p.F877L (c.2629T>C) in gene AR cause the resistance of Apalutamide by aberration of the drug's therapeutic target

Key Molecule: Androgen receptor (AR)

[40]

Resistant Disease

Prostate cancer [ICD-11: 2C82.0]

Resistant Drug

Apalutamide

Drug Info

Molecule Alteration

Missense mutation

p.F877L (c.2629T>C)

Molecule Info

Wild Type Structure

Method: X-ray diffraction

Resolution: 1.44 Å

PDB: 5V8Q

Mutant Type Structure

Method: X-ray diffraction

Resolution: 1.69 Å

PDB: 8FH1

Download The Information of Sequence

Download The Structure File

Click to Show/Hide the Structure

Experimental Note

Revealed Based on the Cell Line Data

In Vitro Model

LNCaP cells

Prostate

Homo sapiens (Human)

CVCL_0395

PC3 cells

Prostate

Homo sapiens (Human)

CVCL_0035

In Vivo Model

SHO male mouse xenograft model

Mus musculus

Experiment for
Molecule Alteration

Chromatin immunoprecipitation assay

Mechanism Description

The missense mutation p.F877L (c.2629T>C) in gene AR cause the resistance of Apalutamide by aberration of the drug's therapeutic target

Key Molecule: Androgen receptor (AR)

[40]

Resistant Disease

Prostate cancer [ICD-11: 2C82.0]

Resistant Drug

Apalutamide

Drug Info

Molecule Alteration

Missense mutation

p.F877L (.

Molecule Info

Experimental Note

Revealed Based on the Cell Line Data

In Vitro Model

LNCaP cells

Prostate

Homo sapiens (Human)

CVCL_0395

PC3 cells

Prostate

Homo sapiens (Human)

CVCL_0035

In Vivo Model

SHO male mouse xenograft model

Mus musculus

Experiment for
Molecule Alteration

Chromatin immunoprecipitation assay

Mechanism Description

The missense mutation p.F877L (. in gene AR cause the resistance of Apalutamide by aberration of the drug's therapeutic target

Metabolic Reprogramming via Altered Pathways (MRAP)

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Key Molecule: Homeodomain-interacting protein kinase 3 (HIPK3)

[41]

Metabolic Type

Mitochondrial metabolism

Resistant Disease

Prostate cancer [ICD-11: 2C82.0]

Resistant Drug

Apalutamide

Drug Info

Molecule Alteration

Molecule Info

Experimental Note

Revealed Based on the Cell Line Data

In Vitro Model

PNT1A cells

Prostate

Homo sapiens (Human)

CVCL_2163

Experiment for
Drug Resistance

Apoptosis rate assay

Mechanism Description

Recently, we have demonstrated that an inhibitor of the mitochondrial electron transport chain complex I IACS-010759 ('IACS') acts synergistically with ARN in reducing PCa cell growth [21]. In this study, we investigated the effects of ARN and IACS on the mitochondrial network architecture and dynamics in PCa cells. Additionally, we explored the effect of androgen in regulating the mitochondrial network dynamics and metabolic modulations of respiratory pathways.

Key Molecule: Homeodomain-interacting protein kinase 3 (HIPK3)

[41]

Metabolic Type

Mitochondrial metabolism

Resistant Disease

Prostate cancer [ICD-11: 2C82.0]

Resistant Drug

Apalutamide

Drug Info

Molecule Alteration

Molecule Info

Experimental Note

Revealed Based on the Cell Line Data

In Vitro Model

LNCaP cells

Prostate

Homo sapiens (Human)

CVCL_0395

Experiment for
Drug Resistance

Apoptosis rate assay

Mechanism Description

Recently, we have demonstrated that an inhibitor of the mitochondrial electron transport chain complex I IACS-010759 ('IACS') acts synergistically with ARN in reducing PCa cell growth [22]. In this study, we investigated the effects of ARN and IACS on the mitochondrial network architecture and dynamics in PCa cells. Additionally, we explored the effect of androgen in regulating the mitochondrial network dynamics and metabolic modulations of respiratory pathways.

Key Molecule: Homeodomain-interacting protein kinase 3 (HIPK3)

[41]

Metabolic Type

Mitochondrial metabolism

Resistant Disease

Prostate cancer [ICD-11: 2C82.0]

Resistant Drug

Apalutamide

Drug Info

Molecule Alteration

Molecule Info

Experimental Note

Revealed Based on the Cell Line Data

In Vitro Model

PC-3 cells

Bone

Homo sapiens (Human)

CVCL_0035

Experiment for
Drug Resistance

Apoptosis rate assay

Mechanism Description

Recently, we have demonstrated that an inhibitor of the mitochondrial electron transport chain complex I IACS-010759 ('IACS') acts synergistically with ARN in reducing PCa cell growth [23]. In this study, we investigated the effects of ARN and IACS on the mitochondrial network architecture and dynamics in PCa cells. Additionally, we explored the effect of androgen in regulating the mitochondrial network dynamics and metabolic modulations of respiratory pathways.

Key Molecule: Homeodomain-interacting protein kinase 3 (HIPK3)

[41]

Metabolic Type

Mitochondrial metabolism

Resistant Disease

Prostate cancer [ICD-11: 2C82.0]

Resistant Drug

Apalutamide

Drug Info

Molecule Alteration

Molecule Info

Experimental Note

Revealed Based on the Cell Line Data

In Vitro Model

C4-2 cells

Prostate

Homo sapiens (Human)

CVCL_4782

Experiment for
Drug Resistance

Apoptosis rate assay

Mechanism Description

Recently, we have demonstrated that an inhibitor of the mitochondrial electron transport chain complex I IACS-010759 ('IACS') acts synergistically with ARN in reducing PCa cell growth [24]. In this study, we investigated the effects of ARN and IACS on the mitochondrial network architecture and dynamics in PCa cells. Additionally, we explored the effect of androgen in regulating the mitochondrial network dynamics and metabolic modulations of respiratory pathways.

Cloperastine

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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Calcium/calmodulin-dependent protein kinase type II subunit delta (CAMK2D)				[44]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]
Sensitive Drug	Cloperastine			Drug Info
Molecule Alteration	Phosphorylation		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Oxytocin signaling pathway		Activation	hsa04921
In Vitro Model	DU145CR cells	prostate	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	MS analysis
Experiment for Drug Resistance	Cell viability assay
Mechanism Description	Pathway analysis revealed that clusters in two cases showed up-regulation of the oxytocin (OXT) receptor-signaling pathway. Spatial gene expression analysis of CBZ-resistant prostate cancer tissues confirmed the heterogeneous expression of OXT-signaling molecules. We identified the OXT-signaling pathway as a potential target for CBZ-resistant CRPC using single-cell transcriptomic analysis of CTCs. CLO may potentially overcome CBZ resistance in CRPC by inhibiting the OXT-signaling pathway.

Enzalutamide

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Aberration of the Drug's Therapeutic Target (ADTT)			Click to Show/Hide
Key Molecule: Androgen receptor (AR)				[39]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Enzalutamide			Drug Info
Molecule Alteration	Structural variation		Copy number gain	Molecule Info
Experimental Note	Identified from the Human Clinical Data
Experiment for Molecule Alteration	Whole genome sequencing assay; Exome sequencing assay
Mechanism Description	Accordingly, AR amplification was detected in circulating cell-free DNA and was shown to be associated with enzalutamide and abiraterone treatment resistance in a cohort of 62 CRPC patients.
Key Molecule: Androgen receptor (AR)				[39]
Resistant Disease	Primary prostate cancer [ICD-11: 2C82.Z]
Resistant Drug	Enzalutamide			Drug Info
Molecule Alteration	Structural variation		Copy number gain	Molecule Info
Experimental Note	Identified from the Human Clinical Data
Experiment for Molecule Alteration	Whole genome sequencing assay; Exome sequencing assay
Mechanism Description	Accordingly, AR amplification was detected in circulating cell-free DNA and was shown to be associated with enzalutamide and abiraterone treatment resistance in a cohort of 62 CRPC patients.
Metabolic Reprogramming via Altered Pathways (MRAP)			Click to Show/Hide
Key Molecule: Solute carrier family 25 member 17 (SLC25A17)				[65]
Metabolic Type	Lipid metabolism
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Enzalutamide			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	C4-2B cells	Prostate	Homo sapiens (Human)	CVCL_4784
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Cell viability assay
Mechanism Description	Mechanistically, silencing of SLC25A17 and SLC27A6 led to the downregulation of FASN and ACC and their downstream metabolic products including triglycerides and lactic acid with a decrease in cell proliferation and migration in C4-2B enzalutamide resistant cells (Figures 5 and 6). Suppression of SLC25A17 and SLC27A6 delays cell cycle progression with the reduction in the protein expression of CyclinD1 and CDK6 in enzalutamide resistant cells (Figures 4 and 5).
Key Molecule: Solute carrier family 27 member 6 (SLC27A6)				[65]
Metabolic Type	Lipid metabolism
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Enzalutamide			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	C4-2B cells	Prostate	Homo sapiens (Human)	CVCL_4784
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Cell viability assay
Mechanism Description	Mechanistically, silencing of SLC25A17 and SLC27A6 led to the downregulation of FASN and ACC and their downstream metabolic products including triglycerides and lactic acid with a decrease in cell proliferation and migration in C4-2B enzalutamide resistant cells (Figures 5 and 6). Suppression of SLC25A17 and SLC27A6 delays cell cycle progression with the reduction in the protein expression of CyclinD1 and CDK6 in enzalutamide resistant cells (Figures 4 and 5).
Key Molecule: Chromosome 3 open reading frame 14 (C3orf14)				[66]
Metabolic Type	Glutamine metabolism
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Enzalutamide			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	C4-2B cells	Prostate	Homo sapiens (Human)	CVCL_4784
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	Cell viability assay
Mechanism Description	We compared the transcriptomic profile of paired enzalutamide-sensitive and resistant LNCaP and C4-11B prostate cancer cells for identification of genes involved in drug resistance by performing an unbiased bioinformatics analysis and further validation
Key Molecule: Chromosome 3 open reading frame 14 (C3orf14)				[66]
Metabolic Type	Glutamine metabolism
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Enzalutamide			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	Cell viability assay
Mechanism Description	We compared the transcriptomic profile of paired enzalutamide-sensitive and resistant LNCaP and C4-2B prostate cancer cells for identification of genes involved in drug resistance by performing an unbiased bioinformatics analysis and further validation

Clinical Trial Drug(s)

4 drug(s) in total

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Canertinib

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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Protransforming growth factor alpha (TGFA)				[2]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]
Sensitive Drug	Canertinib			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate cancer
The Studied Tissue	Blood
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 8.36E-10 Fold-change: 1.90E-01 Z-score: 6.41E+00
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell migration		Activation	hsa04670
	Cell proliferation		Activation	hsa05200
	EGFR/RAS signaling pathway		Activation	hsa01521
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Promega assay
Mechanism Description	The induction of bone metastasis and TkI resistance require miR-203 down-regulation, activation of the EGFR pathway via altered expression of EGFR ligands (EREG and TGFA) and anti-apoptotic proteins (API5, BIRC2, and TRIAP1). Importantly, a sufficient reconstitution of invasiveness and resistance to TkIs treatment was observed in cells transfected with anti-miR-203. In prostate cancer patients, miR-203 levels were inversely correlated with the expression of two EGFR ligands, EREG and TGFA, and an EGFR dependent gene signature.
Key Molecule: Proepiregulin (EREG)				[2]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]
Sensitive Drug	Canertinib			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate cancer
The Studied Tissue	Blood
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 7.31E-11 Fold-change: 7.13E-01 Z-score: 6.92E+00
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell migration		Activation	hsa04670
	Cell proliferation		Activation	hsa05200
	EGFR/RAS signaling pathway		Activation	hsa01521
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Promega assay
Mechanism Description	The induction of bone metastasis and TkI resistance require miR-203 down-regulation, activation of the EGFR pathway via altered expression of EGFR ligands (EREG and TGFA) and anti-apoptotic proteins (API5, BIRC2, and TRIAP1). Importantly, a sufficient reconstitution of invasiveness and resistance to TkIs treatment was observed in cells transfected with anti-miR-203. In prostate cancer patients, miR-203 levels were inversely correlated with the expression of two EGFR ligands, EREG and TGFA, and an EGFR dependent gene signature.
Key Molecule: Amphiregulin (AREG)				[2]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]
Sensitive Drug	Canertinib			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate cancer
The Studied Tissue	Prostate
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 3.00E-02 Fold-change: 1.62E-01 Z-score: 2.30E+00
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell migration		Activation	hsa04670
	Cell proliferation		Activation	hsa05200
	EGFR/RAS signaling pathway		Activation	hsa01521
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Promega assay
Mechanism Description	The induction of bone metastasis and TkI resistance require miR-203 down-regulation, activation of the EGFR pathway via altered expression of EGFR ligands (EREG and TGFA) and anti-apoptotic proteins (API5, BIRC2, and TRIAP1). Importantly, a sufficient reconstitution of invasiveness and resistance to TkIs treatment was observed in cells transfected with anti-miR-203. In prostate cancer patients, miR-203 levels were inversely correlated with the expression of two EGFR ligands, EREG and TGFA, and an EGFR dependent gene signature.

Trichostatin A

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Endoplasmic reticulum chaperone BiP (HSPA5)				[18]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Trichostatin A			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate cancer
The Studied Tissue	Prostate
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 3.92E-01 Fold-change: 1.27E-02 Z-score: 8.69E-01
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
In Vitro Model	C4-2B cells	Prostate	Homo sapiens (Human)	CVCL_4784
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	GRP78 up-regulation is a major contributor to tumorigenesis and therapeutic resistance, miR-30d, miR-181a and miR-199a-5p regulate GRP78 and that their decreased expression in tumor cells results in increased GRP78 levels, which in turn promotes tumorigenesis and therapeutic resistance.

Camptothecin

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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: NAD-dependent protein deacetylase sirtuin-1 (SIRT1)				[23]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]
Sensitive Drug	Camptothecin			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate cancer
The Studied Tissue	Prostate
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 7.32E-01 Fold-change: -1.01E-02 Z-score: -3.46E-01
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell growth		Inhibition	hsa05200
	Cell proliferation		Inhibition	hsa05200
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
	PrEC cells	Prostate	Homo sapiens (Human)	CVCL_0061
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Trypan blue dye exclusion assay
Mechanism Description	Inhibition of the SIRT1 activity or expression resulted in attenuation of cell proliferation and chemoresistance in PC3 and DU145 cells. Ectopic expression of miR-34a decreased the SIRT1 mRNA and protein levels as well as protein levels of known direct target genes. Ectopic miR-34a expression resulted in cell cycle arrest and growth inhibition and attenuated chemoresistance to anticancer drug camptothecin by inducing apoptosis.

Genistein

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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: HOX transcript antisense RNA (HOTAIR)				[34]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]
Sensitive Drug	Genistein			Drug Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate adenocarcinoma
The Studied Tissue	Prostate
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 1.52E-06 Fold-change: -2.11E+00 Z-score: -5.01E+00
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell migration		Inhibition	hsa04670
	Cell proliferation		Inhibition	hsa05200
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_0395
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
	RWPE-1 cells	Prostate	Homo sapiens (Human)	CVCL_3791
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTS assay
Mechanism Description	Knockdown (siRNA) of HOTAIR decreased PCa cell proliferation, migration and invasion and induced apoptosis and cell cycle arrest. miR-34a was also up-regulated by genistein and may directly target HOTAIR in both PC3 and DU145 PCa cells.

Investigative Drug(s)

2 drug(s) in total

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Tyrphostin AG-1478

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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Protransforming growth factor alpha (TGFA)				[2]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]
Sensitive Drug	Tyrphostin AG-1478			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate cancer
The Studied Tissue	Blood
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 8.36E-10 Fold-change: 1.90E-01 Z-score: 6.41E+00
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell migration		Activation	hsa04670
	Cell proliferation		Activation	hsa05200
	EGFR/RAS signaling pathway		Activation	hsa01521
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Promega assay
Mechanism Description	The induction of bone metastasis and TkI resistance require miR-203 down-regulation, activation of the EGFR pathway via altered expression of EGFR ligands (EREG and TGFA) and anti-apoptotic proteins (API5, BIRC2, and TRIAP1). Importantly, a sufficient reconstitution of invasiveness and resistance to TkIs treatment was observed in cells transfected with anti-miR-203. In prostate cancer patients, miR-203 levels were inversely correlated with the expression of two EGFR ligands, EREG and TGFA, and an EGFR dependent gene signature.
Key Molecule: Proepiregulin (EREG)				[2]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]
Sensitive Drug	Tyrphostin AG-1478			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate cancer
The Studied Tissue	Blood
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 7.31E-11 Fold-change: 7.13E-01 Z-score: 6.92E+00
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell migration		Activation	hsa04670
	Cell proliferation		Activation	hsa05200
	EGFR/RAS signaling pathway		Activation	hsa01521
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Promega assay
Mechanism Description	The induction of bone metastasis and TkI resistance require miR-203 down-regulation, activation of the EGFR pathway via altered expression of EGFR ligands (EREG and TGFA) and anti-apoptotic proteins (API5, BIRC2, and TRIAP1). Importantly, a sufficient reconstitution of invasiveness and resistance to TkIs treatment was observed in cells transfected with anti-miR-203. In prostate cancer patients, miR-203 levels were inversely correlated with the expression of two EGFR ligands, EREG and TGFA, and an EGFR dependent gene signature.
Key Molecule: Amphiregulin (AREG)				[2]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]
Sensitive Drug	Tyrphostin AG-1478			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate cancer
The Studied Tissue	Blood
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 1.10E-17 Fold-change: 3.99E-01 Z-score: 9.35E+00
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell migration		Activation	hsa04670
	Cell proliferation		Activation	hsa05200
	EGFR/RAS signaling pathway		Activation	hsa01521
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Promega assay
Mechanism Description	The induction of bone metastasis and TkI resistance require miR-203 down-regulation, activation of the EGFR pathway via altered expression of EGFR ligands (EREG and TGFA) and anti-apoptotic proteins (API5, BIRC2, and TRIAP1). Importantly, a sufficient reconstitution of invasiveness and resistance to TkIs treatment was observed in cells transfected with anti-miR-203. In prostate cancer patients, miR-203 levels were inversely correlated with the expression of two EGFR ligands, EREG and TGFA, and an EGFR dependent gene signature.

Gardiquimod

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Irregularity in Drug Uptake and Drug Efflux (IDUE)			Click to Show/Hide
Key Molecule: Multidrug resistance protein 1 (ABCB1)				[6]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]
Resistant Drug	Gardiquimod			Drug Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Prostate cancer [ICD-11: 2C82]
The Specified Disease	Prostate cancer
The Studied Tissue	Prostate
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 2.55E-01 Fold-change: 5.35E-02 Z-score: 1.16E+00
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	Hep3B cells	Liver	Homo sapiens (Human)	CVCL_0326
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Resazurin Cell Viability Assay
Mechanism Description	Imidazoquinolines IMQ, RSQ, and GDQ are substrates for P-gp and begins to elucidate differences in their trafficking in cancer cells as a consequence of acquired drug resistance. We believe this work that begins to examine imidazoquinoline trafficking will prove useful in the future rational design of immunotherapeutics with enhanced susceptibility to P-gp efflux that enable increased bioavailability, in MDR cancers.

References

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Prof. Feng ZHU (zhufeng@zju.edu.cn)