Drug Information

Drug (ID: DG00159) and It's Reported Resistant Information

• Name: Cyclophosphamide
• Synonyms: ASTA; Ciclofosfamida; Ciclophosphamide; Clafen; Claphene; Cycloblastin; Cyclophosphamid; Cyclophosphamides; Cyclophosphamidum; Cyclophosphan; Cyclophosphane; Cyclophosphanum; Cyclophosphoramide; Cyclostin; Cyklofosfamid; Cytophosphan; Cytophosphane; Cytoxan; Endoxan; Endoxana; Endoxanal; Endoxane; Enduxan; Genoxal; Mitoxan; Neosar; Procytox; Revimmune; Semdoxan; Sendoxan; Senduxan; Zyklophosphamid; Ciclophosphamide [INN]; Cyclophosphamide Sterile; Cyclophosphamide anhydrous; Cyklofosfamid [Czech]; Cytoxan Lyoph; Endoxan R; Lyophilized Cytoxan; Zyklophosphamid [German]; ASTA B518; Asta B 518; B 518; C 0768; CB 4564; SK 20501; B-518; CB-4564; Ciclofosfamida [INN-Spanish]; Cyclophosphamide (INN); Cyclophosphamide (TN); Cyclophosphamide (anhydrous form); Cyclophosphamide (anhydrous); Cyclophosphamidum [INN-Latin]; Cytoxan (TN); Endoxan (TN); Endoxan-Asta; Neosar (TN); Occupation, cyclophosphamide exposure; Procytox (TN); Revimmune (TN); Bis(2-Chloroethyl)phosphami de cyclic propanolamide; Bis(2-Chloroethyl)phosphamide cyclic propanolamide ester; Bis(2-chloroethyl)phosphoramide cyclic propanolamide ester; D,L-Cyclophosphamide; Cyclophosphamide, (+-)-Isomer; N,N-Bis(2-chloroethyl)-1,3,2-oxazaphosphinan-2-amine 2-oxide; (+-)-Cyclophosphamide; (-)-Cyclophosphamide; (RS)-Cyclophosphamide; 1-(bis(2-chloroethyl)amino)-1-oxo-2-aza-5-oxaphosphoridine; 1-Bis(2-chloroethyl)amino-1-oxo-2-aza-5-oxaphosphoridin; 4-Hydroxy-cyclophosphan-mamophosphatide
• Indication:
  In total 1 Indication(s)
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (6 diseases)
  Breast cancer [ICD-11: 2C60]; [2]
  Diffuse large B-cell lymphoma [ICD-11: 2A81]; [3]
  Hodgkin lymphoma [ICD-11: 2B30]; [4]
  Lung cancer [ICD-11: 2C25]; [5]
  Mature T-cell lymphoma [ICD-11: 2A90]; [6]
  Peritoneal cancer [ICD-11: 2C51]; [7]
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (2 diseases)
  Colon cancer [ICD-11: 2B90]; [8]
  Pancreatic cancer [ICD-11: 2C10]; [8]
• Target: Human Deoxyribonucleic acid (hDNA); NOUNIPROTAC; [1]
• Formula: C7H15Cl2N2O2P
• IsoSMILES: C1CNP(=O)(OC1)N(CCCl)CCCl
• InChI: 1S/C7H15Cl2N2O2P/c8-2-5-11(6-3-9)14(12)10-4-1-7-13-14/h1-7H2,(H,10,12)
• InChIKey: CMSMOCZEIVJLDB-UHFFFAOYSA-N
• PubChem CID: 2907
• ChEBI ID: CHEBI:4027
• TTD Drug ID: D0CT9C
• VARIDT ID: DR00425
• INTEDE ID: DR0391
• DrugBank ID: DB00531

Type(s) of Resistant Mechanism of This Drug

  DISM: Drug Inactivation by Structure Modification

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  RTDM: Regulation by the Disease Microenvironment

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Brain cancer [ICD-11: 2A00]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-129 [9]

• Molecule Alteration: Expression; Up-regulation
• Sensitive Disease: Neuroblastoma [ICD-11: 2A00.11]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell cycle; Inhibition; hsa04110
• In Vitro Model: IMR-32 cells; Abdomen; Homo sapiens (Human); CVCL_0346
• In Vitro Model: BE-M17 cells; Adrenal; Homo sapiens (Human); N.A.
• In Vitro Model: Kelly cells; Adrenal; Homo sapiens (Human); CVCL_2092
• In Vitro Model: NB-1643 cells; Adrenal; Homo sapiens (Human); CVCL_5627
• In Vitro Model: NB1 cells; Adrenal; Homo sapiens (Human); CVCL_1440
• In Vitro Model: NBSD cells; Adrenal; Homo sapiens (Human); CVCL_LF68
• In Vitro Model: Neuro-2a cells; Adrenal; Homo sapiens (Human); CVCL_0470
• In Vitro Model: Sk-N-AS cells; Adrenal; Homo sapiens (Human); CVCL_1700
• In Vitro Model: Sk-N-SH cells; Adrenal; Homo sapiens (Human); CVCL_0531
• In Vitro Model: Sk-SY-5Y cells; Adrenal; Homo sapiens (Human); N.A.
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: miR-129 suppressed cell growth and potentiated chemosensitivity by inhibiting MYO10.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Unconventional myosin-X (MYO10) [9]

• Molecule Alteration: Expression; Down-regulation
• Sensitive Disease: Neuroblastoma [ICD-11: 2A00.11]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell colony; Inhibition; hsa05200
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: IMR-32 cells; Abdomen; Homo sapiens (Human); CVCL_0346
• In Vitro Model: BE-M17 cells; Adrenal; Homo sapiens (Human); N.A.
• In Vitro Model: Kelly cells; Adrenal; Homo sapiens (Human); CVCL_2092
• In Vitro Model: NB-1643 cells; Adrenal; Homo sapiens (Human); CVCL_5627
• In Vitro Model: NB1 cells; Adrenal; Homo sapiens (Human); CVCL_1440
• In Vitro Model: NBSD cells; Adrenal; Homo sapiens (Human); CVCL_LF68
• In Vitro Model: Neuro-2a cells; Adrenal; Homo sapiens (Human); CVCL_0470
• In Vitro Model: Sk-N-AS cells; Adrenal; Homo sapiens (Human); CVCL_1700
• In Vitro Model: Sk-N-SH cells; Adrenal; Homo sapiens (Human); CVCL_0531
• In Vitro Model: Sk-SY-5Y cells; Adrenal; Homo sapiens (Human); N.A.
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis; RIP assay; Luciferase reporter assay
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: miR-129 suppressed cell growth and potentiated chemosensitivity by inhibiting MYO10.

Diffuse large B-cell lymphoma [ICD-11: 2A81]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-148b [3]

• Molecule Alteration: Acetylation; Down-regulation
• Resistant Disease: Diffuse large B-cell lymphoma [ICD-11: 2A81.0]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• Cell Pathway Regulation: HDAC6/miR148b/Ezrin signaling pathway; Regulation; hsa05206
• In Vitro Model: CRL2631 cells; Bone marrow; Homo sapiens (Human); CVCL_3611
• In Vitro Model: CRL2631/CHOP cells; Bone marrow; Homo sapiens (Human); CVCL_3611
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: The high level of HDAC6 inhibited miR-148b via maintaining the low acetylation of histones H3 and H4 in the miR-148b promoter, thus rescuing Ezrin expression and promoting CHOP resistance in DLBCL.

Regulation by the Disease Microenvironment (RTDM)

Key Molecule: hsa-miR-125b-5p [10]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Diffuse large B-cell lymphoma [ICD-11: 2A81.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: SU-DHL-2 cells; Pleural effusion; Homo sapiens (Human); CVCL_9550
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: Expression levels of exosomal miR-99a-5p/miR-125b-5p & their correlation with clinicopathological features in DLBCL patients, the expression levels of miR-99a-5p and miR-125b-5p were significantly higher in the chemoresistant group than in the chemosensitive group.

Key Molecule: hsa-miR-99a-5p [10]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Diffuse large B-cell lymphoma [ICD-11: 2A81.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: SU-DHL-2 cells; Pleural effusion; Homo sapiens (Human); CVCL_9550
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: Expression levels of exosomal miR-99a-5p/miR-125b-5p & their correlation with clinicopathological features in DLBCL patients, the expression levels of miR-99a-5p and miR-125b-5p were significantly higher in the chemoresistant group than in the chemosensitive group.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Ezrin (EZR) [3]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Diffuse large B-cell lymphoma [ICD-11: 2A81.0]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• Cell Pathway Regulation: HDAC6/miR148b/Ezrin signaling pathway; Regulation; hsa05206
• In Vitro Model: CRL2631 cells; Bone marrow; Homo sapiens (Human); CVCL_3611
• In Vitro Model: CRL2631/CHOP cells; Bone marrow; Homo sapiens (Human); CVCL_3611
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: The high level of HDAC6 inhibited miR-148b via maintaining the low acetylation of histones H3 and H4 in the miR-148b promoter, thus rescuing Ezrin expression and promoting CHOP resistance in DLBCL.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-21 [11]

• Molecule Alteration: Expression; Down-regulation
• Sensitive Disease: Diffuse large B-cell lymphoma [ICD-11: 2A81.0]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Inhibition; hsa04151
• In Vitro Model: CRL2631 cells; Bone marrow; Homo sapiens (Human); CVCL_3611
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-21 impacts the PI3k/AkT signaling pathway through the regulation of PTEN, thereby affecting cellular sensitivity to the CHOP chemotherapeutic regimen.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Phosphatase and tensin homolog (PTEN) [11]

• Molecule Alteration: Expression; Up-regulation
• Sensitive Disease: Diffuse large B-cell lymphoma [ICD-11: 2A81.0]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Inhibition; hsa04151
• In Vitro Model: CRL2631 cells; Bone marrow; Homo sapiens (Human); CVCL_3611
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-21 impacts the PI3k/AkT signaling pathway through the regulation of PTEN, thereby affecting cellular sensitivity to the CHOP chemotherapeutic regimen.

Mature T-cell lymphoma [ICD-11: 2A90]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-187 [6]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Peripheral T-cell lymphoma [ICD-11: 2A90.0]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: MOLT4 cells; Bone marrow; Homo sapiens (Human); CVCL_0013
• In Vitro Model: HUT78 cells; Lymph; Homo sapiens (Human); CVCL_0337
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR187 downregulated tumor suppressor gene disabled homolog-2 (Dab2), decreased the interaction of Dab2 with adapter protein Grb2, resulting in Ras activation, phosphorylation/activation of extracellular signal-regulated kinase (ERk) and AkT, and subsequent stabilization of MYC oncoprotein. MiR187-overexpressing cells were resistant to chemotherapeutic agents like doxorubicin, cyclophosphamide, cisplatin and gemcitabine, but sensitive to the proteasome inhibitor bortezomib.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Regulation by the Disease Microenvironment (RTDM)

Key Molecule: Maternally expressed 3 (MEG3) [1]

• Molecule Alteration: Expression; Up-regulation
• Sensitive Disease: Peripheral T-cell lymphoma [ICD-11: 2A90.0]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: PI3K/mTOR signaling pathway; Inhibition; hsa04151
• In Vitro Model: Jurkat cells; Pleural effusion; Homo sapiens (Human); CVCL_0065
• In Vitro Model: SUP-T1 cells; Pleural effusion; Homo sapiens (Human); CVCL_1714
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay; Colony formation assays
• Mechanism Description: MEG3 promotes the drug sensitivity of T-LBL to chemotherapeutic agents by affecting the PI3k/mTOR pathway.

Colon cancer [ICD-11: 2B90]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Cytochrome P450 family 3 subfamily A member1 (CYP3A4) [8]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Colon carcinoma [ICD-11: 2B90.2]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: LS-180 cells; Colon; Homo sapiens (Human); CVCL_0397
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: Sulforhodamine B assay
• Mechanism Description: CYP3A4 is the most abundant hepatic and intestinal cytochrome P450 enzyme in humans, contributing to the metabolism of various drugs such as benzodiazepines, HIV antivirals, macrolide antibiotics, and statins. CYP3A4 3'UTR-luciferase activity was significantly decreased in human embryonic kidney 293 cells transfected with plasmid that expressed microRNA-27b (miR-27b) or mouse microRNA-298 (mmu-miR-298), overexpression of miR-27b or mmu-miR-298 in PANC1 cells led to a lower sensitivity to cyclophosphamide.

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-27b [8]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Colon carcinoma [ICD-11: 2B90.2]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: LS-180 cells; Colon; Homo sapiens (Human); CVCL_0397
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Sulforhodamine B assay
• Mechanism Description: CYP3A4 is the most abundant hepatic and intestinal cytochrome P450 enzyme in humans, contributing to the metabolism of various drugs such as benzodiazepines, HIV antivirals, macrolide antibiotics, and statins. CYP3A4 3'UTR-luciferase activity was significantly decreased in human embryonic kidney 293 cells transfected with plasmid that expressed microRNA-27b (miR-27b) or mouse microRNA-298 (mmu-miR-298), overexpression of miR-27b or mmu-miR-298 in PANC1 cells led to a lower sensitivity to cyclophosphamide.

Pancreatic cancer [ICD-11: 2C10]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Cytochrome P450 family 3 subfamily A member1 (CYP3A4) [8]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Pancreatic cancer [ICD-11: 2C10.3]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Panc1 cells; Pancreas; Homo sapiens (Human); CVCL_0480
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: Sulforhodamine B assay
• Mechanism Description: CYP3A4 is the most abundant hepatic and intestinal cytochrome P450 enzyme in humans, contributing to the metabolism of various drugs such as benzodiazepines, HIV antivirals, macrolide antibiotics, and statins. CYP3A4 3'UTR-luciferase activity was significantly decreased in human embryonic kidney 293 cells transfected with plasmid that expressed microRNA-27b (miR-27b) or mouse microRNA-298 (mmu-miR-298), overexpression of miR-27b or mmu-miR-298 in PANC1 cells led to a lower sensitivity to cyclophosphamide.

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-27b [8]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Pancreatic cancer [ICD-11: 2C10.3]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Panc1 cells; Pancreas; Homo sapiens (Human); CVCL_0480
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Sulforhodamine B assay
• Mechanism Description: CYP3A4 is the most abundant hepatic and intestinal cytochrome P450 enzyme in humans, contributing to the metabolism of various drugs such as benzodiazepines, HIV antivirals, macrolide antibiotics, and statins. CYP3A4 3'UTR-luciferase activity was significantly decreased in human embryonic kidney 293 cells transfected with plasmid that expressed microRNA-27b (miR-27b) or mouse microRNA-298 (mmu-miR-298), overexpression of miR-27b or mmu-miR-298 in PANC1 cells led to a lower sensitivity to cyclophosphamide.

Lung cancer [ICD-11: 2C25]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Regulation by the Disease Microenvironment (RTDM)

Key Molecule: ATPase H+ transporting V0 subunit d1 (ATP6V0D1) [5]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Non-small cell lung cancer [ICD-11: 2C25.Y]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Non-small cell lung cancer isolates; Lung; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Immunofluorescence assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The drug resistance of cancer cells is likely to be related to the changes in pH gradient between the extracellular environment and the cytoplasm.Vacuolar-H+ -ATPase(V-ATPase) plays a major role in the regulation of cellular pH conditions.The expression of V-ATPase was shown to be related to the pathological type and grade of the cancer and might be associated with the chemotherapy drug resistance in NSCLC.

Key Molecule: ATPase H+ transporting V0 subunit d1 (ATP6V0D1) [5]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Lung squamous cell carcinoma [ICD-11: 2C25.3]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Non-small cell lung cancer isolates; Lung; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Immunofluorescence assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The drug resistance of cancer cells is likely to be related to the changes in pH gradient between the extracellular environment and the cytoplasm.Vacuolar-H+ -ATPase(V-ATPase) plays a major role in the regulation of cellular pH conditions.The expression of V-ATPase was shown to be related to the pathological type and grade of the cancer and might be associated with the chemotherapy drug resistance in NSCLC.

Key Molecule: ATPase H+ transporting V0 subunit d1 (ATP6V0D1) [5]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Non-small cell lung cancer [ICD-11: 2C25.Y]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Non-small cell lung cancer isolates; Lung; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Immunofluorescence assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The drug resistance of cancer cells is likely to be related to the changes in pH gradient between the extracellular environment and the cytoplasm.Vacuolar-H+ -ATPase(V-ATPase) plays a major role in the regulation of cellular pH conditions.The expression of V-ATPase was shown to be related to the pathological type and grade of the cancer and might be associated with the chemotherapy drug resistance in NSCLC.

Breast cancer [ICD-11: 2C60]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-204 [12]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Low miR-024 expression was enhancing chemotherapeutic resistance of breast cancer patients.

Key Molecule: hsa-mir-125b [2], [13]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: p53 signaling pathway; Inhibition; hsa04115
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: T47D cells; Breast; Homo sapiens (Human); CVCL_0553
• In Vitro Model: BT20 cells; Breast; Homo sapiens (Human); CVCL_0178
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Sphere formation assay
• Mechanism Description: E2F3, and in some settings E2F1, induce apoptosis through p53-dependent or -independent pathways, Overexpression of miR-125b in MCF-7 cells significantly down-regulated E2F3 protein level, overexpression of miR-125b caused a marked inhibition of anticancer drug activity and increased resistance in breast cancer cells in vitro. And elevated miR-125b expression in chemoresistant cancer cells were due to high percentage of SP cells.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Transcription factor E2F3 (E2F3) [2]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: p53 signaling pathway; Inhibition; hsa04115
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: T47D cells; Breast; Homo sapiens (Human); CVCL_0553
• In Vitro Model: BT20 cells; Breast; Homo sapiens (Human); CVCL_0178
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Trypan blue dye exclusion assay
• Mechanism Description: E2F3, and in some settings E2F1, induce apoptosis through p53-dependent or -independent pathways, Overexpression of miR-125b in MCF-7 cells significantly down-regulated E2F3 protein level, overexpression of miR-125b caused a marked inhibition of anticancer drug activity and increased resistance in breast cancer cells in vitro.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-205 [14]

• Molecule Alteration: Expression; Up-regulation
• Sensitive Disease: Breast cancer [ICD-11: 2C60.3]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Regulation; hsa04151
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Drug resistance clonogenic assay
• Mechanism Description: miR-205 enhances chemosensitivity of breast cancer cells to TAC chemotherapy by suppressing both VEGFA and FGF2, leading to evasion of apoptosis.

Key Molecule: hsa-mir-663 [15]

• Molecule Alteration: Expression; Down-regulation
• Sensitive Disease: Breast cancer [ICD-11: 2C60.3]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: BT474 cells; Breast; Homo sapiens (Human); CVCL_0179
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: TUNEL analysis
• Mechanism Description: Overexpression of hypomethylated miR-663 induced chemoresistance in breast cancer cells by down-regulating HSPG2.

Regulation by the Disease Microenvironment (RTDM)

Key Molecule: hsa-mir-200a [16]

• Molecule Alteration: Expression; Up-regulation
• Sensitive Disease: Breast cancer [ICD-11: 2C60.3]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: Tri-PyMT cells; Breast; Homo sapiens (Human); N.A.
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CellTiter-Glo luminescent cell viability assay
• Mechanism Description: Inhibiting EMT by overexpressing miR-200 did not impact lung metastasis development. However, EMT cells significantly contribute to recurrent lung metastasis formation after chemotherapy. These cells survived cyclophosphamide treatment due to reduced proliferation, apoptotic tolerance, and elevated expression of chemoresistance-related genes. Overexpression of miR-200 abrogated this resistance.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Fibroblast growth factor 2 (FGF1) [14]

• Molecule Alteration: Expression; Down-regulation
• Sensitive Disease: Breast cancer [ICD-11: 2C60.3]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Regulation; hsa04151
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Drug resistance clonogenic assay
• Mechanism Description: miR-205 enhances chemosensitivity of breast cancer cells to TAC chemotherapy by suppressing both VEGFA and FGF2, leading to evasion of apoptosis.

Key Molecule: Vascular endothelial growth factor A (VEGFA) [14]

• Molecule Alteration: Expression; Down-regulation
• Sensitive Disease: Breast cancer [ICD-11: 2C60.3]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Regulation; hsa04151
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Drug resistance clonogenic assay
• Mechanism Description: miR-205 enhances chemosensitivity of breast cancer cells to TAC chemotherapy by suppressing both VEGFA and FGF2, leading to evasion of apoptosis.

Key Molecule: Heparan sulfate proteoglycan 2 (HSPG2) [15]

• Molecule Alteration: Expression; Down-regulation
• Sensitive Disease: Breast cancer [ICD-11: 2C60.3]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: BT474 cells; Breast; Homo sapiens (Human); CVCL_0179
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: TUNEL analysis
• Mechanism Description: Overexpression of hypomethylated miR-663 induced chemoresistance in breast cancer cells by down-regulating HSPG2.

Ovarian cancer [ICD-11: 2C73]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-29b [17]

• Molecule Alteration: Expression; Up-regulation
• Sensitive Disease: Ovarian cancer [ICD-11: 2C73.0]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: miR29b signaling pathway; Regulation; hsa05206
• In Vitro Model: OVCAR3 cells; Ovary; Homo sapiens (Human); CVCL_0465
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: H&E staining assay
• Mechanism Description: The ATG9A down expression due to miR-29b increasing could significantly promote Ovarian carcinoma drug sensitivity on different chemotherapeutic drugs (Cisplatin, Paclitaxel, Platinum, Cyclophosphamide).

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Autophagy-related protein 9A (ATG9A) [17]

• Molecule Alteration: Expression; Down-regulation
• Sensitive Disease: Ovarian cancer [ICD-11: 2C73.0]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: miR29b signaling pathway; Regulation; hsa05206
• In Vitro Model: OVCAR3 cells; Ovary; Homo sapiens (Human); CVCL_0465
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: H&E staining assay
• Mechanism Description: The ATG9A down expression due to miR-29b increasing could significantly promote Ovarian carcinoma drug sensitivity on different chemotherapeutic drugs (Cisplatin, Paclitaxel, Platinum, Cyclophosphamide).

References

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