Disease Information

General Information of the Disease (ID: DIS00198)

Name	Unclassified pleomorphic sarcoma
ICD	ICD-11: 2B54
Resistance Map

Type(s) of Resistant Mechanism of This Disease

UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Investigative Drug(s)

2 drug(s) in total

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GDC-0623

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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: GTPase HRas (HRAS)				[1]
Resistant Disease	Unclassified pleomorphic sarcoma [ICD-11: 2B54.0]
Molecule Alteration	Missense mutation		p.G12V	Molecule Info
Resistant Drug	GDC-0623			Drug Info
Experimental Note	Discovered Using In-vivo Testing Model
Cell Pathway Regulation	RAS signaling pathway		Activation	hsa04014
In Vitro Model	HEK293T cells	Kidney	Homo sapiens (Human)	CVCL_0063
	NIH3T3 cells	Embryo	Homo sapiens (Human)	N.A.
In Vivo Model	SCID/Beige mice model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR; Western blotting assay
Experiment for Drug Resistance	Cell viability assay
Mechanism Description	Hras G12V mutation changed the drug target,impairing the ability to inhibit RAS-RAF-MEK-ERK signaling.

SCH772984

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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: GTPase HRas (HRAS)				[1]
Resistant Disease	Unclassified pleomorphic sarcoma [ICD-11: 2B54.0]
Molecule Alteration	Missense mutation		p.G12V	Molecule Info
Resistant Drug	SCH772984			Drug Info
Experimental Note	Discovered Using In-vivo Testing Model
Cell Pathway Regulation	RAS signaling pathway		Activation	hsa04014
In Vitro Model	HEK293T cells	Kidney	Homo sapiens (Human)	CVCL_0063
	NIH3T3 cells	Embryo	Homo sapiens (Human)	N.A.
In Vivo Model	SCID/Beige mice model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR; Western blotting assay
Experiment for Drug Resistance	Cell viability assay
Mechanism Description	Hras G12V mutation changed the drug target,impairing the ability to inhibit RAS-RAF-MEK-ERK signaling.

References

Ref 1	Sensitivity and Resistance of Oncogenic RAS-Driven Tumors to Dual MEK and ERK Inhibition .Cancers (Basel). 2021 Apr 13;13(8):1852. doi: 10.3390/cancers13081852. 10.3390/cancers13081852