Disease Information

General Information of the Disease (ID: DIS00221)

Type(s) of Resistant Mechanism of This Disease

ADTT: Aberration of the Drug's Therapeutic Target

UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s)

2 drug(s) in total

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Dabrafenib/Trametinib

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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Aberration of the Drug's Therapeutic Target (ADTT)		Click to Show/Hide
Key Molecule: Serine/threonine-protein kinase B-raf (BRAF)			[1]
Sensitive Disease	Salivary gland adenoid cystic carcinoma [ICD-11: 2E60.0]
Molecule Alteration	Missense mutation	p.V600E (c.1799T>A)	Molecule Info
Sensitive Drug	Dabrafenib/Trametinib		Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Human laryngeal cells isolates		.
Experiment for Molecule Alteration	ctDNA sequencing assay

Fluorouracil

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Prominin-1 (PROM1)				[2]
Resistant Disease	Salivary gland adenoid cystic carcinoma [ICD-11: 2E60.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Fluorouracil			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	MET/PI3K/AKT/mTOR signaling pathway		Activation	hsa04150
	Cell migration		Activation	hsa04670
	Cell invasion		Activation	hsa05200
In Vitro Model	KOA-1 cells	Skin	Homo sapiens (Human)	CVCL_L997
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	CCK-8 assay
Mechanism Description	CD133 activates the PI3K/AKT, AKT/Wnt and other signaling pathways and affects the behavior of CD133+ cells, thereby playing a major role in cancer therapy. In addition, CD133 is also involved in the regulation of tumor resistance. Long-term chemotherapy leads to a significant increase in CD133 expression. Targeting CD133 can reverse drug resistance in colorectal cancer via the AKT/NF-kappa-B/multidrug resistance protein (MDR)1 pathway.

Investigative Drug(s)

1 drug(s) in total

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Pingyangmycin

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Prominin-1 (PROM1)				[2]
Resistant Disease	Salivary gland adenoid cystic carcinoma [ICD-11: 2E60.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Pingyangmycin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	MET/PI3K/AKT/mTOR signaling pathway		Activation	hsa04150
	Cell migration		Activation	hsa04670
	Cell invasion		Activation	hsa05200
In Vitro Model	KOA-1 cells	Skin	Homo sapiens (Human)	CVCL_L997
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	CCK-8 assay
Mechanism Description	CD133 activates the PI3K/AKT, AKT/Wnt and other signaling pathways and affects the behavior of CD133+ cells, thereby playing a major role in cancer therapy. In addition, CD133 is also involved in the regulation of tumor resistance. Long-term chemotherapy leads to a significant increase in CD133 expression. Targeting CD133 can reverse drug resistance in colorectal cancer via the AKT/NF-kappa-B/multidrug resistance protein (MDR)1 pathway.

References

Ref 1	First-Line Treatment of Widely Metastatic BRAF-Mutated Salivary Duct Carcinoma With Combined BRAF and MEK InhibitionJ Natl Compr Canc Netw. 2018 Oct;16(10):1166-1170. doi: 10.6004/jnccn.2018.7056.
Ref 2	Effects of CD133 expression on chemotherapy and drug sensitivity of adenoid cystic carcinoma .Mol Med Rep. 2022 Jan;25(1):18. doi: 10.3892/mmr.2021.12534. Epub 2021 Nov 18. 10.3892/mmr.2021.12534