Drug Information

Drug (ID: DG00346) and It's Reported Resistant Information

Name	Trastuzumab
Synonyms	Herceptin; Herceptin (TN); Trastuzumab (INN); Trastuzumab (genetical recombination); Trastuzumab (genetical recombination) (JAN); Trastuzumab (ERBB2 mAb inhibitor) Click to Show/Hide
Indication	In total 2 Indication(s) Breast cancer [ICD-11: 2C60] Approved [1] Stomach cancer [ICD-11: 2B72] Application submitted [1]
Drug Resistance Disease(s)	Disease(s) with Clinically Reported Resistance for This Drug (1 diseases) Breast cancer [ICD-11: 2C60] [2] Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (2 diseases) Breast cancer [ICD-11: 2C60] [3] Gastric cancer [ICD-11: 2B72] [4]
Target	Erbb2 tyrosine kinase receptor (HER2)	ERBB2_HUMAN	[1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
TTD Drug ID	D04WFL
DrugBank ID	DB00072

Type(s) of Resistant Mechanism of This Drug

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

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Gastric cancer [ICD-11: 2B72]

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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: hsa-mir-223				[5]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Disease	Gastric cancer [ICD-11: 2B72.1]			Disease Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell proliferation		Activation	hsa05200
	miR223/FBXW7 signaling pathway		Regulation	hsa05206
In Vitro Model	NCI-N87 cells	Gastric	Homo sapiens (Human)	CVCL_1603
	MkN-45 cells	Gastric	Homo sapiens (Human)	CVCL_0434
	KATO-3 cells	Gastric	Homo sapiens (Human)	CVCL_0371
	NUGC3 cells	Gastric	Homo sapiens (Human)	CVCL_1612
	NUGC4 cells	Gastric	Homo sapiens (Human)	CVCL_3082
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay
Mechanism Description	Overexpression of miR-223 decreased FBXW7 expression and the sensitivity of GC cells to trastuzumab, while suppression of miR-223 restored FBXW7 expression and the sensitivity of GC cells to trastuzumab.
Key Molecule: hsa-mir-21				[4]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Disease	Gastric cancer [ICD-11: 2B72.1]			Disease Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
Cell Pathway Regulation	miR21/PTEN signaling pathway		Activation	hsa05206
In Vitro Model	NCI-N87 cells	Gastric	Homo sapiens (Human)	CVCL_1603
	MkN-45 cells	Gastric	Homo sapiens (Human)	CVCL_0434
	NUGC4 cells	Gastric	Homo sapiens (Human)	CVCL_3082
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	The miR-21/PTEN pathway regulated the sensitivity of HER2-positive GC cell lines to trastuzumab through modulation apoptosis.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: F-box/WD repeat-containing protein 7 (FBXW7)				[5]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Disease	Gastric cancer [ICD-11: 2B72.1]			Disease Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell proliferation		Activation	hsa05200
	miR223/FBXW7 signaling pathway		Regulation	hsa05206
In Vitro Model	NCI-N87 cells	Gastric	Homo sapiens (Human)	CVCL_1603
	MkN-45 cells	Gastric	Homo sapiens (Human)	CVCL_0434
	KATO-3 cells	Gastric	Homo sapiens (Human)	CVCL_0371
	NUGC3 cells	Gastric	Homo sapiens (Human)	CVCL_1612
	NUGC4 cells	Gastric	Homo sapiens (Human)	CVCL_3082
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay
Mechanism Description	Overexpression of miR-223 decreased FBXW7 expression and the sensitivity of GC cells to trastuzumab, while suppression of miR-223 restored FBXW7 expression and the sensitivity of GC cells to trastuzumab.
Key Molecule: Phosphatase and tensin homolog (PTEN)				[4]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Disease	Gastric cancer [ICD-11: 2B72.1]			Disease Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
Cell Pathway Regulation	miR21/PTEN signaling pathway		Activation	hsa05206
In Vitro Model	NCI-N87 cells	Gastric	Homo sapiens (Human)	CVCL_1603
	MkN-45 cells	Gastric	Homo sapiens (Human)	CVCL_0434
	NUGC4 cells	Gastric	Homo sapiens (Human)	CVCL_3082
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	The miR-21/PTEN pathway regulated the sensitivity of HER2-positive GC cell lines to trastuzumab through modulation apoptosis.

Breast cancer [ICD-11: 2C60]

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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: H19, imprinted maternally expressed transcript (H19)				[1]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	Higher expression of H19 might lead to trastuzumab resistance in HER2-positive breast cancer patients. High H19 expression was associated with a worse clinical prognosis and a lower PFS.
Key Molecule: hsa-miR-141-3p				[6]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell invasion		Activation	hsa05200
	Cell migration		Activation	hsa04670
	Cell proliferation		Activation	hsa05200
	miR141-3p/CDk8 signaling pathway		Inhibition	hsa05206
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
	MDA-MB-231 cells	Breast	Homo sapiens (Human)	CVCL_0062
	HEK293T cells	Kidney	Homo sapiens (Human)	CVCL_0063
Experiment for Molecule Alteration	qPCR
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay
Mechanism Description	miR-141-3p could restore the sensitivity to trastuzumab in breast cancer cells by repressing CDk8, which might regulate the phosphorylation levels of SMAD2/SMAD3 via TGF-beta.
Key Molecule: Small nucleolar RNA host gene 14 (SNHG14)				[7]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell colony		Activation	hsa05200
	Cell invasion		Activation	hsa05200
	Cell migration		Activation	hsa04670
	Cell viability		Activation	hsa05200
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
	BT474 cells	Breast	Homo sapiens (Human)	CVCL_0179
In Vivo Model	BALB/c nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	Long non-coding RNA SNHG14 induces trastuzumab resistance of breast cancer via inducing PABPC1 expression through H3k27 acetylation.
Key Molecule: Small nucleolar RNA host gene 14 (SNHG14)				[8]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	BCL2/Bax apoptosis signaling pathway		Activation	hsa04210
	Cell invasion		Inhibition	hsa05200
	Cell metabolism		Inhibition	hsa01100
	Cell migration		Inhibition	hsa04670
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
	BT474 cells	Breast	Homo sapiens (Human)	CVCL_0179
Experiment for Molecule Alteration	RT-qPCR
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay
Mechanism Description	Exosomal LncRNA-SNHG14 may induce trastuzumab resistance through inhibiting apoptotic proteins and cell apoptosis via Bcl-2/Bax pathway.
Key Molecule: hsa-mir-182				[9]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell autophagy		Inhibition	hsa04140
	MET/PI3K/AKT/mTOR signaling pathway		Activation	hsa04150
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
	BT474 cells	Breast	Homo sapiens (Human)	CVCL_0179
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	MTS assay; Transwell assay
Mechanism Description	Overexpression of miR-182 reduced trastuzumab resistance in trastuzumab-resistant cells due in part to MET/PI3k/AkT/mTOR signaling pathway inactivation.
Key Molecule: Urothelial cancer associated 1 (UCA1)				[10]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell invasion		Activation	hsa05200
	Cell viability		Activation	hsa05200
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
Experiment for Molecule Alteration	qPCR
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay; Matrigel Invasion assay
Mechanism Description	UCA1 knockdown upregulated miR-18a and downregulated YAP1 in breast cancer cells, restoring sensitivity of breast cancer cells to trastuzumab.
Key Molecule: Growth arrest specific 5 (GAS5)				[11]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell proliferation		Activation	hsa05200
	mTOR signaling pathway		Activation	hsa04150
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	Down-regulation of LncRNA GAS5 causes trastuzumab resistance in breast cancer.Expression of the LncRNA GAS5 was decreased in trastuzumab-resistant SkBR-3/Tr cells and in breast cancer tissue from trastuzumab-treated patients. GAS5 suppresses cancer proliferation by acting as a molecular sponge for miR-21, leading to the de-repression of phosphatase and tensin homologs (PTEN), the endogenous target of miR-21. Moreover, mTOR activation associated with reduced GAS5 expression was required to suppress PTEN. This work identifies GAS5 as a novel prognostic marker and candidate drug target for HER2-positive breast cancer.
Key Molecule: hsa-mir-21				[12]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	PI3K signaling pathway		Activation	hsa04151
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	A target prediction analysis coupled with in vitro and in vivo validations revealed that miR-21 levels inversely correlated with the expression of PTEN and PDCD4, which differentially influenced the drug sensitivity of HER2-positive breast cancer cells.miR-21 was able to affect the response to both trastuzumab and chemotherapy, triggering an IL-6/STAT3/NF-kB-mediated signaling loop and activating the PI3k pathway. These findings support the ability of miR-21 signaling to sustain EMT and shape the tumor immune microenvironment in HER2-positive breast cancer.
Key Molecule: Long non-protein coding RNA (Lnc-ATB)				[13]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease 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 proliferation		Activation	hsa05200
	TGF-beta signaling pathway		Regulation	hsa04350
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
Experiment for Molecule Alteration	qPCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	Lnc-ATB is up-regulated in TR breast cancer tissues and TR SkBR-3 cells. Up-regulation of lnc-ATB account for the trastuzumab resistance and high invasiveness of TR SkBR-3 cells. miR-200c is down-regulated and inverse correlated with lnc-ATB in TR breast cancer tissues and TR SkBR-3 cells. Lnc-ATB functions as a ceRNA by competitively biding miR-200c in TR SkBR-3 cells. Lnc-ATB up-regulates and positive correlates with ZEB1 and ZNF217 levels.
Key Molecule: hsa-mir-200c				[13]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease 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 proliferation		Activation	hsa05200
	TGF-beta signaling pathway		Regulation	hsa04350
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	Lnc-ATB is up-regulated in TR breast cancer tissues and TR SkBR-3 cells. Up-regulation of lnc-ATB account for the trastuzumab resistance and high invasiveness of TR SkBR-3 cells. miR-200c is down-regulated and inverse correlated with lnc-ATB in TR breast cancer tissues and TR SkBR-3 cells. Lnc-ATB functions as a ceRNA by competitively biding miR-200c in TR SkBR-3 cells. Lnc-ATB up-regulates and positive correlates with ZEB1 and ZNF217 levels.
Key Molecule: hsa-miR-542-3p				[3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell proliferation		Activation	hsa05200
	PI3K/AKT signaling pathway		Inhibition	hsa04151
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
	MCF7/HER2 cells	Breast	Homo sapiens (Human)	CVCL_0U80
Experiment for Molecule Alteration	RT-qPCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	Trastuzumab induced miRNA 542 3p expression in SkBR3 and MCF7/Her2 cells. Furthermore, knockdown of miRNA 542 3p in the two cell lines resulted in decreased drug sensitivity to trastuzumab and cell apoptosis. The blockage of G1/S checkpoint by trastuzumab was rescued as well. miRNA 542 3p knockdown also activated the phosphatidylinositol 3 kinase (PI3k) Akt pathway, while LY294002 reversed the effect of miRNA 542 3p knockdown. In summary, the results suggested that miRNA 542 3p downregulation may contribute to the trastuzumab resistance in breast cancer via, at least in part, the PI3k akt pathway.
Key Molecule: hsa-mir-375				[14]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	PI3K/AKT signaling pathway		Activation	hsa04151
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
In Vivo Model	BALB/c nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	Insulin-like growth factor-1 receptor (IGF1R) is thought to play a key role in the acquisition of cancer resistance to trastuzumab and other targeted pharmaceuticals. Epigenetic silencing of miR-375 causes the upregulation of IGF1R, which at least partially underlies trastuzumab resistance of breast cancer cells.
Key Molecule: hsa-mir-221				[15]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell migration		Activation	hsa04670
	Cell proliferation		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	miR-221 promotes the invasiveness and trastuzumab resistance of HER2-positive breast cancers by targeting the tumor suppressor gene PTEN.
Key Molecule: hsa-mir-210				[16]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	BT474 cells	Breast	Homo sapiens (Human)	CVCL_0179
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	Clonogenic assay
Mechanism Description	The function of miR-210, which is directly regulated by hypoxia-inducible factor 1-alpha, may also depend on cancer type. miR-210 inhibits apoptosis, bypasses cell-cycle arrest, and promotes cancer cell survival when overexpressed, but when underexpressed, as it is in esophageal squamous cell carcinoma, it represses the initiation of tumor growth by inducing cell death and cell-cycle arrest.
Key Molecule: hsa-mir-21				[2]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	AKT signaling pathway		Activation	hsa04151
	Cell proliferation		Activation	hsa05200
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
	BT474 cells	Breast	Homo sapiens (Human)	CVCL_0179
	MDA-MB-453 cells	Breast	Homo sapiens (Human)	CVCL_0418
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	RT-PCR; Northern blotting analysis
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	PTEN is a tumor suppressing dual phosphatase that antagonizes the function of phosphatidylinositol 3-kinase (PI3k) and negatively regulates AkT activities, and PTEN phosphorylation is a crucial mechanism mediating the anti-tumor effect of trastuzumab by reducing and inhibiting the ErbB2 receptor-bound SRC. Ectopic expression of miR-21 in the previously sensitive cells confers trastuzumab resistance via PTEN inhibition.
Key Molecule: TINCR ubiquitin domain containing (TINCR)				[17]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell invasion		Activation	hsa05200
	Cell migration		Activation	hsa04670
In Vitro Model	Lunet cells	hepato	Homo sapiens (Human)	CVCL_U459
	Pseudomonas aeruginosa strain B-730P/17			287
In Vivo Model	BALB/c nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	Activation of LncRNA TINCR by H3K27 acetylation promotes trastuzumab resistance and epithelial-mesenchymal transition by targeting MicroRNA-125b in breast cancer.
Regulation by the Disease Microenvironment (RTDM)			Click to Show/Hide
Key Molecule: Zinc finger protein SNAI1 (SNAI1)				[17]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease 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
	miR125b/HER2/Snail1 signaling pathway		Regulation	hsa05206
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
	BT474 cells	Breast	Homo sapiens (Human)	CVCL_0179
In Vivo Model	BALB/c nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay; Wound-healing assay; Transwell assay
Mechanism Description	TINCR, which is transcriptionally activated by H3k27 acetylation, upregulates HER-2 expression by downregulating miR-125b and TINCR promotes trastuzumab resistance-induced EMT by directly targeting Snail-1.
Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2)				[17]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell invasion		Activation	hsa05200
	Cell migration		Activation	hsa04670
	Cell viability		Inhibition	hsa05200
	miR125b/HER2/Snail1 signaling pathway		Regulation	hsa05206
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
	BT474 cells	Breast	Homo sapiens (Human)	CVCL_0179
In Vivo Model	BALB/c nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay; Wound-healing assay; Transwell assay
Mechanism Description	TINCR, which is transcriptionally activated by H3k27 acetylation, upregulates HER-2 expression by downregulating miR-125b and TINCR promotes trastuzumab resistance-induced EMT by directly targeting Snail-1.
Key Molecule: hsa-mir-125b				[17]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell invasion		Activation	hsa05200
	Cell migration		Activation	hsa04670
	Cell viability		Inhibition	hsa05200
	miR125b/HER2/Snail1 signaling pathway		Regulation	hsa05206
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
	BT474 cells	Breast	Homo sapiens (Human)	CVCL_0179
In Vivo Model	BALB/c nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay; Wound-healing assay; Transwell assay
Mechanism Description	TINCR, which is transcriptionally activated by H3k27 acetylation, upregulates HER-2 expression by downregulating miR-125b and TINCR promotes trastuzumab resistance-induced EMT by directly targeting Snail-1.
Key Molecule: TINCR ubiquitin domain containing (TINCR)				[17]
Molecule Alteration	Acetylation		Up-regulation	Molecule Info
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell invasion		Activation	hsa05200
	Cell migration		Activation	hsa04670
	Cell viability		Inhibition	hsa05200
	miR125b/HER2/Snail1 signaling pathway		Regulation	hsa05206
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
	BT474 cells	Breast	Homo sapiens (Human)	CVCL_0179
In Vivo Model	BALB/c nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay; Wound-healing assay; Transwell assay
Mechanism Description	TINCR, which is transcriptionally activated by H3k27 acetylation, upregulates HER-2 expression by downregulating miR-125b and TINCR promotes trastuzumab resistance-induced EMT by directly targeting Snail-1.
Key Molecule: AGAP2 antisense RNA 1 (AGAP2-AS1)				[18]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell colony		Activation	hsa05200
	Cell proliferation		Activation	hsa05200
	NF-kappaB signaling pathway		Activation	hsa04064
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
	BT474 cells	Breast	Homo sapiens (Human)	CVCL_0179
In Vivo Model	BALB/c nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	RT-qPCR
Experiment for Drug Resistance	MTT assay; TUNEL assay
Mechanism Description	AGAP2-AS1 could promote breast cancer growth and trastuzumab resistance by activating the NF-kB signaling pathway and upregulating MyD88 expression.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Cyclin-dependent kinase 8 (CDK8)				[6]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell invasion		Activation	hsa05200
	Cell migration		Activation	hsa04670
	Cell proliferation		Activation	hsa05200
	miR141-3p/CDk8 signaling pathway		Inhibition	hsa05206
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
	MDA-MB-231 cells	Breast	Homo sapiens (Human)	CVCL_0062
	HEK293T cells	Kidney	Homo sapiens (Human)	CVCL_0063
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay
Mechanism Description	miR-141-3p could restore the sensitivity to trastuzumab in breast cancer cells by repressing CDk8, which might regulate the phosphorylation levels of SMAD2/SMAD3 via TGF-beta.
Key Molecule: Myeloid differentiation primary response protein MyD88 (MYD88)				[18]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell migration		Activation	hsa04670
	Cell proliferation		Activation	hsa05200
	NF-kappaB signaling pathway		Activation	hsa04064
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
	BT474 cells	Breast	Homo sapiens (Human)	CVCL_0179
In Vivo Model	BALB/c nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay; TUNEL assay
Mechanism Description	AGAP2-AS1 could promote breast cancer growth and trastuzumab resistance by activating the NF-kB signaling pathway and upregulating MyD88 expression.
Key Molecule: Polyadenylate-binding protein 1 (PABPC1)				[7]
Molecule Alteration	Acetylation		Up-regulation	Molecule Info
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease 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	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
	BT474 cells	Breast	Homo sapiens (Human)	CVCL_0179
In Vivo Model	BALB/c nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	Long non-coding RNA SNHG14 induces trastuzumab resistance of breast cancer via inducing PABPC1 expression through H3k27 acetylation.
Key Molecule: Apoptosis regulator Bcl-2 (BCL2)				[8]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	BCL2/Bax apoptosis signaling pathway		Activation	hsa04210
	Cell apoptosis		Inhibition	hsa04210
	Cell invasion		Activation	hsa05200
	Cell viability		Activation	hsa05200
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
	BT474 cells	Breast	Homo sapiens (Human)	CVCL_0179
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay
Mechanism Description	Exosomal LncRNA-SNHG14 may induce trastuzumab resistance through inhibiting apoptotic proteins and cell apoptosis via Bcl-2/Bax pathway.
Key Molecule: Hepatocyte growth factor receptor (MET)				[9]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell invasion		Activation	hsa05200
	Cell viability		Activation	hsa05200
	MET/PI3K/AKT/mTOR signaling pathway		Activation	hsa04150
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
	BT474 cells	Breast	Homo sapiens (Human)	CVCL_0179
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; Transwell assay
Mechanism Description	Overexpression of miR-182 reduced trastuzumab resistance in trastuzumab-resistant cells due in part to MET/PI3k/AkT/mTOR signaling pathway inactivation.
Key Molecule: Transcriptional coactivator YAP1 (YAP1)				[10]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell invasion		Activation	hsa05200
	Cell viability		Activation	hsa05200
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay; Matrigel Invasion assay
Mechanism Description	UCA1 knockdown upregulated miR-18a and downregulated YAP1 in breast cancer cells, restoring sensitivity of breast cancer cells to trastuzumab.
Key Molecule: Phosphatase and tensin homolog (PTEN)				[11]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell proliferation		Activation	hsa05200
	mTOR signaling pathway		Activation	hsa04150
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
Experiment for Molecule Alteration	Western blot analysis; Flow cytometric assay
Experiment for Drug Resistance	MTT assay
Mechanism Description	Down-regulation of LncRNA GAS5 causes trastuzumab resistance in breast cancer.Expression of the LncRNA GAS5 was decreased in trastuzumab-resistant SkBR-3/Tr cells and in breast cancer tissue from trastuzumab-treated patients. GAS5 suppresses cancer proliferation by acting as a molecular sponge for miR-21, leading to the de-repression of phosphatase and tensin homologs (PTEN), the endogenous target of miR-21. Moreover, mTOR activation associated with reduced GAS5 expression was required to suppress PTEN. This work identifies GAS5 as a novel prognostic marker and candidate drug target for HER2-positive breast cancer.
Key Molecule: Programmed cell death protein 4 (PDCD4)				[12]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	PI3K signaling pathway		Activation	hsa04151
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	A target prediction analysis coupled with in vitro and in vivo validations revealed that miR-21 levels inversely correlated with the expression of PTEN and PDCD4, which differentially influenced the drug sensitivity of HER2-positive breast cancer cells.miR-21 was able to affect the response to both trastuzumab and chemotherapy, triggering an IL-6/STAT3/NF-kB-mediated signaling loop and activating the PI3k pathway. These findings support the ability of miR-21 signaling to sustain EMT and shape the tumor immune microenvironment in HER2-positive breast cancer.
Key Molecule: Phosphatase and tensin homolog (PTEN)				[12]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	PI3K signaling pathway		Activation	hsa04151
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	A target prediction analysis coupled with in vitro and in vivo validations revealed that miR-21 levels inversely correlated with the expression of PTEN and PDCD4, which differentially influenced the drug sensitivity of HER2-positive breast cancer cells.miR-21 was able to affect the response to both trastuzumab and chemotherapy, triggering an IL-6/STAT3/NF-kB-mediated signaling loop and activating the PI3k pathway. These findings support the ability of miR-21 signaling to sustain EMT and shape the tumor immune microenvironment in HER2-positive breast cancer.
Key Molecule: Zinc finger E-box-binding homeobox 1 (ZEB1)				[13]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease 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 proliferation		Activation	hsa05200
	TGF-beta signaling pathway		Regulation	hsa04350
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	Lnc-ATB is up-regulated in TR breast cancer tissues and TR SkBR-3 cells. Up-regulation of lnc-ATB account for the trastuzumab resistance and high invasiveness of TR SkBR-3 cells. miR-200c is down-regulated and inverse correlated with lnc-ATB in TR breast cancer tissues and TR SkBR-3 cells. Lnc-ATB functions as a ceRNA by competitively biding miR-200c in TR SkBR-3 cells. Lnc-ATB up-regulates and positive correlates with ZEB1 and ZNF217 levels.
Key Molecule: Zinc finger protein 217 (ZNF217)				[13]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease 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 proliferation		Activation	hsa05200
	TGF-beta signaling pathway		Regulation	hsa04350
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	Lnc-ATB is up-regulated in TR breast cancer tissues and TR SkBR-3 cells. Up-regulation of lnc-ATB account for the trastuzumab resistance and high invasiveness of TR SkBR-3 cells. miR-200c is down-regulated and inverse correlated with lnc-ATB in TR breast cancer tissues and TR SkBR-3 cells. Lnc-ATB functions as a ceRNA by competitively biding miR-200c in TR SkBR-3 cells. Lnc-ATB up-regulates and positive correlates with ZEB1 and ZNF217 levels.
Key Molecule: Phosphatase and tensin homolog (PTEN)				[2], [15]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	AKT signaling pathway		Activation	hsa04151
	Cell apoptosis		Inhibition	hsa04210
	Cell migration		Activation	hsa04670
	Cell proliferation		Activation	hsa05200
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
	BT474 cells	Breast	Homo sapiens (Human)	CVCL_0179
	MDA-MB-453 cells	Breast	Homo sapiens (Human)	CVCL_0418
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	MTT assay; Flow cytometry assay
Mechanism Description	PTEN is a tumor suppressing dual phosphatase that antagonizes the function of phosphatidylinositol 3-kinase (PI3k) and negatively regulates AkT activities, and PTEN phosphorylation is a crucial mechanism mediating the anti-tumor effect of trastuzumab by reducing and inhibiting the ErbB2 receptor-bound SRC. Ectopic expression of miR-21 in the previously sensitive cells confers trastuzumab resistance via PTEN inhibition. And miR-221 promotes the invasiveness and trastuzumab resistance of HER2-positive breast cancers by targeting the tumor suppressor gene PTEN.
Key Molecule: Insulin-like growth factor 1 receptor (IGF1R)				[14]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	PI3K/AKT signaling pathway		Activation	hsa04151
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
In Vivo Model	BALB/c nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Luciferase reporter assay
Experiment for Drug Resistance	MTT assay
Mechanism Description	Insulin-like growth factor-1 receptor (IGF1R) is thought to play a key role in the acquisition of cancer resistance to trastuzumab and other targeted pharmaceuticals. Epigenetic silencing of miR-375 causes the upregulation of IGF1R, which at least partially underlies trastuzumab resistance of breast cancer cells.
Key Molecule: Mediator of RNA polymerase II transcription subunit 1 (MED1)				[19]
Molecule Alteration	Missense mutation		p.S1179X	Molecule Info
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	AXLK signaling pathway		Activation	hsa01521
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Circulating-free DNA assay; Whole exome sequencing assay
Mechanism Description	Quantification of allele fractions in plasma identified increased representation of mutant alleles in association with emergence of therapy resistance.
Key Molecule: Serine-protein kinase ATM (ATM)				[19]
Molecule Alteration	Missense mutation		p.I2948F	Molecule Info
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	AXLK signaling pathway		Activation	hsa01521
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Circulating-free DNA assay; Whole exome sequencing assay
Mechanism Description	Quantification of allele fractions in plasma identified increased representation of mutant alleles in association with emergence of therapy resistance.
Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA)				[19]
Molecule Alteration	Missense mutation		p.D714E	Molecule Info
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	AKT signaling pathway		Activation	hsa04151
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Circulating-free DNA assay; Whole exome sequencing assay
Mechanism Description	Quantification of allele fractions in plasma identified increased representation of mutant alleles in association with emergence of therapy resistance.
Key Molecule: Epidermal growth factor receptor (EGFR)				[20]
Molecule Alteration	Missense mutation		p.V292E	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Next-generation sequencing assay; Circulating-free DNA assay
Experiment for Drug Resistance	Positron emission tomography/Computed tomography assay
Mechanism Description	Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Epidermal growth factor receptor (EGFR)				[20]
Molecule Alteration	Missense mutation		p.I706T	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Next-generation sequencing assay; Circulating-free DNA assay
Experiment for Drug Resistance	Positron emission tomography/Computed tomography assay
Mechanism Description	Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Neurogenic locus notch homolog protein 1 (NOTCH1)				[20]
Molecule Alteration	Missense mutation		p.V1599M	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Notch signaling pathway		Regulation	hsa04330
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Next-generation sequencing assay; Circulating-free DNA assay
Experiment for Drug Resistance	Positron emission tomography/Computed tomography assay
Mechanism Description	Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Neurogenic locus notch homolog protein 1 (NOTCH1)				[20]
Molecule Alteration	Missense mutation		p.S1689P	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Notch signaling pathway		Regulation	hsa04330
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Next-generation sequencing assay; Circulating-free DNA assay
Experiment for Drug Resistance	Positron emission tomography/Computed tomography assay
Mechanism Description	Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: GTPase Nras (NRAS)				[20]
Molecule Alteration	Missense mutation		p.V14A	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Next-generation sequencing assay; Circulating-free DNA assay
Experiment for Drug Resistance	Positron emission tomography/Computed tomography assay
Mechanism Description	Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: GTPase Nras (NRAS)				[20]
Molecule Alteration	Missense mutation		p.F78L	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Next-generation sequencing assay; Circulating-free DNA assay
Experiment for Drug Resistance	Positron emission tomography/Computed tomography assay
Mechanism Description	Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: GTPase Nras (NRAS)				[20]
Molecule Alteration	Missense mutation		p.F28S	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Next-generation sequencing assay; Circulating-free DNA assay
Experiment for Drug Resistance	Positron emission tomography/Computed tomography assay
Mechanism Description	Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: GTPase Nras (NRAS)				[20]
Molecule Alteration	Missense mutation		p.A66T	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Next-generation sequencing assay; Circulating-free DNA assay
Experiment for Drug Resistance	Positron emission tomography/Computed tomography assay
Mechanism Description	Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: DNA mismatch repair protein Mlh1 (MLH1)				[20]
Molecule Alteration	Missense mutation		p.V345A	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Next-generation sequencing assay; Circulating-free DNA assay
Experiment for Drug Resistance	Positron emission tomography/Computed tomography assay
Mechanism Description	Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: DNA mismatch repair protein Mlh1 (MLH1)				[20]
Molecule Alteration	Missense mutation		p.R90Q	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Next-generation sequencing assay; Circulating-free DNA assay
Experiment for Drug Resistance	Positron emission tomography/Computed tomography assay
Mechanism Description	Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: DNA mismatch repair protein Mlh1 (MLH1)				[20]
Molecule Alteration	Missense mutation		p.R74Q	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Next-generation sequencing assay; Circulating-free DNA assay
Experiment for Drug Resistance	Positron emission tomography/Computed tomography assay
Mechanism Description	Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: DNA mismatch repair protein Mlh1 (MLH1)				[20]
Molecule Alteration	Missense mutation		p.A348V	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Next-generation sequencing assay; Circulating-free DNA assay
Experiment for Drug Resistance	Positron emission tomography/Computed tomography assay
Mechanism Description	Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: GTPase Hras (HRAS)				[20]
Molecule Alteration	Missense mutation		p.V9A	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Next-generation sequencing assay; Circulating-free DNA assay
Experiment for Drug Resistance	Positron emission tomography/Computed tomography assay
Mechanism Description	Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: GTPase Hras (HRAS)				[20]
Molecule Alteration	Missense mutation		p.T2A	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Next-generation sequencing assay; Circulating-free DNA assay
Experiment for Drug Resistance	Positron emission tomography/Computed tomography assay
Mechanism Description	Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: GTPase Hras (HRAS)				[20]
Molecule Alteration	Missense mutation		p.S17N	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Next-generation sequencing assay; Circulating-free DNA assay
Experiment for Drug Resistance	Positron emission tomography/Computed tomography assay
Mechanism Description	Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: GTPase Hras (HRAS)				[20]
Molecule Alteration	Missense mutation		p.Q61X	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Next-generation sequencing assay; Circulating-free DNA assay
Experiment for Drug Resistance	Positron emission tomography/Computed tomography assay
Mechanism Description	Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: GTPase Hras (HRAS)				[20]
Molecule Alteration	Missense mutation		p.N26S	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Next-generation sequencing assay; Circulating-free DNA assay
Experiment for Drug Resistance	Positron emission tomography/Computed tomography assay
Mechanism Description	Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: GTPase Hras (HRAS)				[20]
Molecule Alteration	Missense mutation		p.G12S	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Next-generation sequencing assay; Circulating-free DNA assay
Experiment for Drug Resistance	Positron emission tomography/Computed tomography assay
Mechanism Description	Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: GTPase Hras (HRAS)				[20]
Molecule Alteration	Missense mutation		p.D54N	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Next-generation sequencing assay; Circulating-free DNA assay
Experiment for Drug Resistance	Positron emission tomography/Computed tomography assay
Mechanism Description	Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Adenylate cyclase-stimulating G alpha protein (GNAS)				[20]
Molecule Alteration	Missense mutation		p.R216L	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Next-generation sequencing assay; Circulating-free DNA assay
Experiment for Drug Resistance	Positron emission tomography/Computed tomography assay
Mechanism Description	Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Adenylate cyclase-stimulating G alpha protein (GNAS)				[20]
Molecule Alteration	Missense mutation		p.R216C	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Next-generation sequencing assay; Circulating-free DNA assay
Experiment for Drug Resistance	Positron emission tomography/Computed tomography assay
Mechanism Description	Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Adenylate cyclase-stimulating G alpha protein (GNAS)				[20]
Molecule Alteration	Missense mutation		p.R186H	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Next-generation sequencing assay; Circulating-free DNA assay
Experiment for Drug Resistance	Positron emission tomography/Computed tomography assay
Mechanism Description	Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Adenylate cyclase-stimulating G alpha protein (GNAS)				[20]
Molecule Alteration	Missense mutation		p.N203S	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Next-generation sequencing assay; Circulating-free DNA assay
Experiment for Drug Resistance	Positron emission tomography/Computed tomography assay
Mechanism Description	Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Adenylate cyclase-stimulating G alpha protein (GNAS)				[20]
Molecule Alteration	Missense mutation		p.M206V	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Next-generation sequencing assay; Circulating-free DNA assay
Experiment for Drug Resistance	Positron emission tomography/Computed tomography assay
Mechanism Description	Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Adenylate cyclase-stimulating G alpha protein (GNAS)				[20]
Molecule Alteration	Missense mutation		p.D214N	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Next-generation sequencing assay; Circulating-free DNA assay
Experiment for Drug Resistance	Positron emission tomography/Computed tomography assay
Mechanism Description	Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Adenylate cyclase-stimulating G alpha protein (GNAS)				[20]
Molecule Alteration	Missense mutation		p.D181G	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Next-generation sequencing assay; Circulating-free DNA assay
Experiment for Drug Resistance	Positron emission tomography/Computed tomography assay
Mechanism Description	Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Epidermal growth factor receptor (EGFR)				[20]
Molecule Alteration	Missense mutation		p.R705G	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Next-generation sequencing assay; Circulating-free DNA assay
Experiment for Drug Resistance	Positron emission tomography/Computed tomography assay
Mechanism Description	Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Epidermal growth factor receptor (EGFR)				[20]
Molecule Alteration	Missense mutation		p.L760F	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Next-generation sequencing assay; Circulating-free DNA assay
Experiment for Drug Resistance	Positron emission tomography/Computed tomography assay
Mechanism Description	Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Epidermal growth factor receptor (EGFR)				[20]
Molecule Alteration	Missense mutation		p.K284E	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Next-generation sequencing assay; Circulating-free DNA assay
Experiment for Drug Resistance	Positron emission tomography/Computed tomography assay
Mechanism Description	Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Epidermal growth factor receptor (EGFR)				[20]
Molecule Alteration	Missense mutation		p.G696E	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Next-generation sequencing assay; Circulating-free DNA assay
Experiment for Drug Resistance	Positron emission tomography/Computed tomography assay
Mechanism Description	Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Epidermal growth factor receptor (EGFR)				[20]
Molecule Alteration	Missense mutation		p.A822V	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Next-generation sequencing assay; Circulating-free DNA assay
Experiment for Drug Resistance	Positron emission tomography/Computed tomography assay
Mechanism Description	Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Epidermal growth factor receptor (EGFR)				[20]
Molecule Alteration	Missense mutation		p.V292M	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Next-generation sequencing assay; Circulating-free DNA assay
Experiment for Drug Resistance	Positron emission tomography/Computed tomography assay
Mechanism Description	Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Epidermal growth factor receptor (EGFR)				[20]
Molecule Alteration	Missense mutation		p.P741S	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Next-generation sequencing assay; Circulating-free DNA assay
Experiment for Drug Resistance	Positron emission tomography/Computed tomography assay
Mechanism Description	Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Epidermal growth factor receptor (EGFR)				[20]
Molecule Alteration	Missense mutation		p.G288D	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Next-generation sequencing assay; Circulating-free DNA assay
Experiment for Drug Resistance	Positron emission tomography/Computed tomography assay
Mechanism Description	Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Epidermal growth factor receptor (EGFR)				[20]
Molecule Alteration	Missense mutation		p.E711K	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Next-generation sequencing assay; Circulating-free DNA assay
Experiment for Drug Resistance	Positron emission tomography/Computed tomography assay
Mechanism Description	Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Cadherin-1 (CDH1)				[20]
Molecule Alteration	Missense mutation		p.R90Q	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Next-generation sequencing assay; Circulating-free DNA assay
Experiment for Drug Resistance	Positron emission tomography/Computed tomography assay
Mechanism Description	Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Cadherin-1 (CDH1)				[20]
Molecule Alteration	Missense mutation		p.A348V	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Next-generation sequencing assay; Circulating-free DNA assay
Experiment for Drug Resistance	Positron emission tomography/Computed tomography assay
Mechanism Description	Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Cadherin-1 (CDH1)				[20]
Molecule Alteration	Missense mutation		p.V345A	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Next-generation sequencing assay; Circulating-free DNA assay
Experiment for Drug Resistance	Positron emission tomography/Computed tomography assay
Mechanism Description	Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Cadherin-1 (CDH1)				[20]
Molecule Alteration	Missense mutation		p.R74Q	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Next-generation sequencing assay; Circulating-free DNA assay
Experiment for Drug Resistance	Positron emission tomography/Computed tomography assay
Mechanism Description	Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: Neurogenic locus notch homolog protein 1 (NOTCH1)				[20]
Molecule Alteration	Missense mutation		p.V1676A	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Notch signaling pathway		Regulation	hsa04330
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Next-generation sequencing assay; Circulating-free DNA assay
Experiment for Drug Resistance	Positron emission tomography/Computed tomography assay
Mechanism Description	Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy.
Key Molecule: PI3-kinase alpha (PIK3CA)				[21]
Molecule Alteration	Missense mutation		p.E545K (c.1633G>A)	Molecule Info
Resistant Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Revealed Based on the Cell Line Data
In Vivo Model	Female athymic nude xenograft model			Mus musculus
Experiment for Molecule Alteration	Immunoblotting analysis
Experiment for Drug Resistance	WST-1 assay
Mechanism Description	The missense mutation p.E545K (c.1633G>A) in gene PIK3CA cause the resistance of Trastuzumab by unusual activation of pro-survival pathway

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: hsa-miR-770-5p				[22]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell invasion		Inhibition	hsa05200
	Cell proliferation		Inhibition	hsa05200
	HER2 signaling pathway		Activation	hsa04012
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
	BT474 cells	Breast	Homo sapiens (Human)	CVCL_0179
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	WST1 assay
Mechanism Description	miR-770-5p overexpression downregulated HER2 and increased the effect of trastuzumab.
Key Molecule: hsa-miR-129-5p				[23]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	PI3K/AKT/mTOR signaling pathway		Inhibition	hsa04151
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
	JIMT-1 cells	Breast	Homo sapiens (Human)	CVCL_2077
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	miR129-5p might inhibit trastuzumab resistance through downregulating rpS6 in Her-2-positive breast cancer cells, thus inactivating the PI3k/Akt/mTOR/ rpS6 pathway.
Key Molecule: hsa-mir-18a				[10]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell invasion		Inhibition	hsa05200
	Cell viability		Inhibition	hsa05200
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay; Matrigel Invasion assay
Mechanism Description	UCA1 knockdown upregulated miR-18a and downregulated YAP1 in breast cancer cells, restoring sensitivity of breast cancer cells to trastuzumab.
Key Molecule: Urothelial cancer associated 1 (UCA1)				[10]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell invasion		Inhibition	hsa05200
	Cell viability		Inhibition	hsa05200
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay; Matrigel Invasion assay
Mechanism Description	UCA1 knockdown upregulated miR-18a and downregulated YAP1 in breast cancer cells, restoring sensitivity of breast cancer cells to trastuzumab.
Key Molecule: hsa-mir-7				[24]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell invasion		Inhibition	hsa05200
	Cell migration		Inhibition	hsa04670
	Cell proliferation		Inhibition	hsa05200
In Vitro Model	MCF-7 cells	Breast	Homo sapiens (Human)	CVCL_0031
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	Colcount colony counter assay
Mechanism Description	miR-7 suppression of HER2deta16 oncogenic activity is mediated through inactivation of Src kinase and suppression of EGFR expression implies that targeting these pathways would also suppress HER2deta16 tumorigenesis. HER2deta16 suppresses expression of the miR-7 tumor suppressor and reestablished miR-7 expression significantly inhibits HER2deta16 mediated tumor cell proliferation and migration and miR-7 sensitizes HER2deta16 expressing cells to trastuzumab treatment.
Key Molecule: hsa-mir-200c				[25]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell invasion		Inhibition	hsa05200
	TGF-Beta/ZEB1 signaling pathway		Inhibition	hsa04350
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	miR-200c, which was the most significantly downregulated miRNA in trastuzumab-resistant cells, restored trastuzumab sensitivity and suppressed invasion of breast cancer cells by concurrently targeting ZNF217, a transcriptional activator of TGF-beta, and ZEB1, a known mediator of TGF-beta signaling. Restoration of miR-200c, silencing of ZEB1 or ZNF217 or blockade of TGF-beta signaling increased trastuzumab sensitivity and suppressed invasiveness of breast cancer cells.
Regulation by the Disease Microenvironment (RTDM)			Click to Show/Hide
Key Molecule: hnRNP A2/B1 (HNRNPA2B1)				[26]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell viability		Inhibition	hsa05200
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
	BT474 cells	Breast	Homo sapiens (Human)	CVCL_0179
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay; TUNEL assay; Flow cytometry assay
Mechanism Description	Exosomal AGAP2-AS1 expression was upregulated by hnRNPA2B1 overexpression and suppressed by hnRNPA2B1 knockdown in SkBR-3R cells while knockdown of AGAP2-AS1 resensitized trastuzumab resistance in breast cancer cells.
Key Molecule: AGAP2 antisense RNA 1 (AGAP2-AS1)				[26]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell viability		Inhibition	hsa05200
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
	BT474 cells	Breast	Homo sapiens (Human)	CVCL_0179
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	CCK8 assay; TUNEL assay; Flow cytometry assay
Mechanism Description	Exosomal AGAP2-AS1 expression was upregulated by hnRNPA2B1 overexpression and suppressed by hnRNPA2B1 knockdown in SkBR-3R cells while knockdown of AGAP2-AS1 resensitized trastuzumab resistance in breast cancer cells.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2)				[22]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Disease	HER2 positive breast cancer [ICD-11: 2C60.8]			Disease Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell invasion		Inhibition	hsa05200
	Cell proliferation		Inhibition	hsa05200
	HER2 signaling pathway		Activation	hsa04012
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
	BT474 cells	Breast	Homo sapiens (Human)	CVCL_0179
Experiment for Molecule Alteration	Western blot analysis; RT-qPCR
Experiment for Drug Resistance	WST1 assay
Mechanism Description	miR-770-5p overexpression downregulated HER2 and increased the effect of trastuzumab.
Key Molecule: Ribosomal protein S6 (RPS6)				[23]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	PI3K/AKT/mTOR signaling pathway		Inhibition	hsa04151
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
	JIMT-1 cells	Breast	Homo sapiens (Human)	CVCL_2077
Experiment for Molecule Alteration	Western blot analysis; Luciferase reporter assay
Experiment for Drug Resistance	MTT assay
Mechanism Description	miR129-5p might inhibit trastuzumab resistance through downregulating rpS6 in Her-2-positive breast cancer cells, thus inactivating the PI3k/Akt/mTOR/ rpS6 pathway.
Key Molecule: Transcriptional coactivator YAP1 (YAP1)				[10]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell invasion		Inhibition	hsa05200
	Cell viability		Inhibition	hsa05200
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay; Matrigel Invasion assay
Mechanism Description	UCA1 knockdown upregulated miR-18a and downregulated YAP1 in breast cancer cells, restoring sensitivity of breast cancer cells to trastuzumab.
Key Molecule: Epidermal growth factor receptor (EGFR)				[24]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell invasion		Inhibition	hsa05200
	Cell migration		Inhibition	hsa04670
	Cell proliferation		Inhibition	hsa05200
In Vitro Model	MCF-7 cells	Breast	Homo sapiens (Human)	CVCL_0031
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Colcount colony counter assay
Mechanism Description	miR-7 suppression of HER2deta16 oncogenic activity is mediated through inactivation of Src kinase and suppression of EGFR expression implies that targeting these pathways would also suppress HER2deta16 tumorigenesis. HER2deta16 suppresses expression of the miR-7 tumor suppressor and reestablished miR-7 expression significantly inhibits HER2deta16 mediated tumor cell proliferation and migration and miR-7 sensitizes HER2deta16 expressing cells to trastuzumab treatment.
Key Molecule: Zinc finger E-box-binding homeobox 1 (ZEB1)				[25]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell invasion		Inhibition	hsa05200
	TGF-Beta/ZEB1 signaling pathway		Inhibition	hsa04350
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	miR-200c, which was the most significantly downregulated miRNA in trastuzumab-resistant cells, restored trastuzumab sensitivity and suppressed invasion of breast cancer cells by concurrently targeting ZNF217, a transcriptional activator of TGF-beta, and ZEB1, a known mediator of TGF-beta signaling. Restoration of miR-200c, silencing of ZEB1 or ZNF217 or blockade of TGF-beta signaling increased trastuzumab sensitivity and suppressed invasiveness of breast cancer cells.
Key Molecule: Zinc finger protein 217 (ZNF217)				[25]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell invasion		Inhibition	hsa05200
	TGF-Beta/ZEB1 signaling pathway		Inhibition	hsa04350
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	miR-200c, which was the most significantly downregulated miRNA in trastuzumab-resistant cells, restored trastuzumab sensitivity and suppressed invasion of breast cancer cells by concurrently targeting ZNF217, a transcriptional activator of TGF-beta, and ZEB1, a known mediator of TGF-beta signaling. Restoration of miR-200c, silencing of ZEB1 or ZNF217 or blockade of TGF-beta signaling increased trastuzumab sensitivity and suppressed invasiveness of breast cancer cells.

References

Ref 1	Correlation between long non-coding RNAs (lncRNAs) H19 expression and trastuzumab resistance in breast cancer. J Cancer Res Ther. 2019;15(4):933-940. doi: 10.4103/jcrt.JCRT_208_19.
Ref 2	Up-regulation of miR-21 mediates resistance to trastuzumab therapy for breast cancer. J Biol Chem. 2011 May 27;286(21):19127-37. doi: 10.1074/jbc.M110.216887. Epub 2011 Apr 6.
Ref 3	MiRNA 542 3p downregulation promotes trastuzumab resistance in breast cancer cells via AKT activation. Oncol Rep. 2015 Mar;33(3):1215-20. doi: 10.3892/or.2015.3713. Epub 2015 Jan 13.
Ref 4	The microRNA-21/PTEN pathway regulates the sensitivity of HER2-positive gastric cancer cells to trastuzumab. Ann Surg Oncol. 2014 Jan;21(1):343-50. doi: 10.1245/s10434-013-3325-7. Epub 2013 Oct 24.
Ref 5	The sensitivity of gastric cancer to trastuzumab is regulated by the miR-223/FBXW7 pathway. Int J Cancer. 2015 Apr 1;136(7):1537-45. doi: 10.1002/ijc.29168. Epub 2014 Sep 11.
Ref 6	The microRNA-141-3p/ CDK8 pathway regulates the chemosensitivity of breast cancer cells to trastuzumab. J Cell Biochem. 2019 Aug;120(8):14095-14106. doi: 10.1002/jcb.28685. Epub 2019 May 14.
Ref 7	Long non-coding RNA SNHG14 induces trastuzumab resistance of breast cancer via regulating PABPC1 expression through H3K27 acetylation. J Cell Mol Med. 2018 Oct;22(10):4935-4947. doi: 10.1111/jcmm.13758. Epub 2018 Jul 31.
Ref 8	Exosome-mediated transfer of lncRNA SNHG14 promotes trastuzumab chemoresistance in breast cancer. Int J Oncol. 2018 Sep;53(3):1013-1026. doi: 10.3892/ijo.2018.4467. Epub 2018 Jul 3.
Ref 9	miR-182 regulates trastuzumab resistance by targeting MET in breast cancer cells. Cancer Gene Ther. 2019 Feb;26(1-2):1-10. doi: 10.1038/s41417-018-0031-4. Epub 2018 Jun 21.
Ref 10	Long non-coding RNA UCA1 desensitizes breast cancer cells to trastuzumab by impeding miR-18a repression of Yes-associated protein 1. Biochem Biophys Res Commun. 2018 Feb 19;496(4):1308-1313. doi: 10.1016/j.bbrc.2018.02.006. Epub 2018 Feb 7.
Ref 11	Downregulation of LncRNA GAS5 causes trastuzumab resistance in breast cancer. Oncotarget. 2016 May 10;7(19):27778-86. doi: 10.18632/oncotarget.8413.
Ref 12	MicroRNA-21 links epithelial-to-mesenchymal transition and inflammatory signals to confer resistance to neoadjuvant trastuzumab and chemotherapy in HER2-positive breast cancer patients. Oncotarget. 2015 Nov 10;6(35):37269-80. doi: 10.18632/oncotarget.5495.
Ref 13	LncRNA-ATB promotes trastuzumab resistance and invasion-metastasis cascade in breast cancer. Oncotarget. 2015 May 10;6(13):11652-63. doi: 10.18632/oncotarget.3457.
Ref 14	Epigenetic silencing of miR-375 induces trastuzumab resistance in HER2-positive breast cancer by targeting IGF1R. BMC Cancer. 2014 Feb 26;14:134. doi: 10.1186/1471-2407-14-134.
Ref 15	MiR-221 promotes trastuzumab-resistance and metastasis in HER2-positive breast cancers by targeting PTEN. BMB Rep. 2014 May;47(5):268-73. doi: 10.5483/bmbrep.2014.47.5.165.
Ref 16	Plasma microRNA 210 levels correlate with sensitivity to trastuzumab and tumor presence in breast cancer patients. Cancer. 2012 May 15;118(10):2603-14. doi: 10.1002/cncr.26565. Epub 2011 Oct 5.
Ref 17	Activation of LncRNA TINCR by H3K27 acetylation promotes Trastuzumab resistance and epithelial-mesenchymal transition by targeting MicroRNA-125b in breast Cancer. Mol Cancer. 2019 Jan 8;18(1):3. doi: 10.1186/s12943-018-0931-9.
Ref 18	SP1-induced lncRNA AGAP2-AS1 expression promotes chemoresistance of breast cancer by epigenetic regulation of MyD88. J Exp Clin Cancer Res. 2018 Aug 29;37(1):202. doi: 10.1186/s13046-018-0875-3.
Ref 19	Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature. 2013 May 2;497(7447):108-12. doi: 10.1038/nature12065. Epub 2013 Apr 7.
Ref 20	Circulating-free DNA Mutation Associated with Response of Targeted Therapy in Human Epidermal Growth Factor Receptor 2-positive Metastatic Breast Cancer. Chin Med J (Engl). 2017 Mar 5;130(5):522-529. doi: 10.4103/0366-6999.200542.
Ref 21	NVP-BEZ235, a dual PI3K/mTOR inhibitor, prevents PI3K signaling and inhibits the growth of cancer cells with activating PI3K mutationsCancer Res. 2008 Oct 1;68(19):8022-30. doi: 10.1158/0008-5472.CAN-08-1385.
Ref 22	Involvement of miR-770-5p in trastuzumab response in HER2 positive breast cancer cells. PLoS One. 2019 Apr 22;14(4):e0215894. doi: 10.1371/journal.pone.0215894. eCollection 2019.
Ref 23	MiR-129-5p Sensitizes the Response of Her-2 Positive Breast Cancer to Trastuzumab by Reducing Rps6. Cell Physiol Biochem. 2017;44(6):2346-2356. doi: 10.1159/000486122. Epub 2017 Dec 15.
Ref 24	MicroRNA-7 inhibits multiple oncogenic pathways to suppress HER2 Delta 16 mediated breast tumorigenesis and reverse trastuzumab resistance. PLoS One. 2014 Dec 22;9(12):e114419. doi: 10.1371/journal.pone.0114419. eCollection 2014.
Ref 25	MiR-200c suppresses TGF-Beta signaling and counteracts trastuzumab resistance and metastasis by targeting ZNF217 and ZEB1 in breast cancer. Int J Cancer. 2014 Sep 15;135(6):1356-68. doi: 10.1002/ijc.28782. Epub 2014 Mar 3.
Ref 26	Increased Expression of Exosomal AGAP2-AS1 (AGAP2 Antisense RNA 1) In Breast Cancer Cells Inhibits Trastuzumab-Induced Cell Cytotoxicity. Med Sci Monit. 2019 Mar 26;25:2211-2220. doi: 10.12659/MSM.915419.

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