Disease Information

General Information of the Disease (ID: DIS00225)

Name	Peripheral nerve sheath tumor
ICD	ICD-11: 2F3Y
Resistance Map

Type(s) of Resistant Mechanism of This Disease

UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s)

3 drug(s) in total

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Cisplatin

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Neurofibromin (NF1)				[1]
Resistant Disease	Peripheral nerve sheath tumor [ICD-11: 2F3Y.1]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Cisplatin			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	RAS signaling pathway		Activation	hsa04014
In Vitro Model	sNF02.2 cells	Lung	Homo sapiens (Human)	CVCL_K280
	Hs 53.T cells	Skin	Homo sapiens (Human)	CVCL_0786
Experiment for Molecule Alteration	qRT-PCR; Western blotting assay
Experiment for Drug Resistance	Ez-Cytox assay
Mechanism Description	High expression of Bcl-xL in the MPNST cells was caused by a decreased transcriptional expression of the NF1 gene. Down-regulation of the NF1 gene by RNA interference (RNAi) induced an increase in Bcl-xL expression and a decrease in its sensitivity to apoptosis in the benign neurofibroma cell line and primary normal cells.

Doxorubicin

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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: Neurofibromin (NF1)				[1]
Resistant Disease	Peripheral nerve sheath tumor [ICD-11: 2F3Y.1]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Doxorubicin			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	RAS signaling pathway		Activation	hsa04014
In Vitro Model	sNF02.2 cells	Lung	Homo sapiens (Human)	CVCL_K280
	Hs 53.T cells	Skin	Homo sapiens (Human)	CVCL_0786
Experiment for Molecule Alteration	qRT-PCR; Western blotting assay
Experiment for Drug Resistance	Ez-Cytox assay
Mechanism Description	High expression of Bcl-xL in the MPNST cells was caused by a decreased transcriptional expression of the NF1 gene. Down-regulation of the NF1 gene by RNA interference (RNAi) induced an increase in Bcl-xL expression and a decrease in its sensitivity to apoptosis in the benign neurofibroma cell line and primary normal cells.

Etoposide

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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: Neurofibromin (NF1)				[1]
Resistant Disease	Peripheral nerve sheath tumor [ICD-11: 2F3Y.1]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Etoposide			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	RAS signaling pathway		Activation	hsa04014
In Vitro Model	sNF02.2 cells	Lung	Homo sapiens (Human)	CVCL_K280
	Hs 53.T cells	Skin	Homo sapiens (Human)	CVCL_0786
Experiment for Molecule Alteration	qRT-PCR; Western blotting assay
Experiment for Drug Resistance	Ez-Cytox assay
Mechanism Description	High expression of Bcl-xL in the MPNST cells was caused by a decreased transcriptional expression of the NF1 gene. Down-regulation of the NF1 gene by RNA interference (RNAi) induced an increase in Bcl-xL expression and a decrease in its sensitivity to apoptosis in the benign neurofibroma cell line and primary normal cells.

Investigative Drug(s)

1 drug(s) in total

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TAK-733

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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: Cyclin-dependent kinase 1 (CDK1)				[2]
Resistant Disease	Plexiform neurofibroma [ICD-11: 2F3Y.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	TAK-733			Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	ipNF9511.bc cells	Embryo	Homo sapiens (Human)	N.A.
	ipNF05.5 cells	Peripheral blood	Homo sapiens (Human)	CVCL_UI71
In Vivo Model	NOD scid gamma mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	RNA sequencing assay
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	Cell cycle gene sets were significantly upregulated in both resistant cell lines, and specifically, resistant cell lines. That is, cell cycle gene sets were significantly upregulated in both resistant cell lines, and specifically, CDK1 gene activation was observed in both resistant cell lines.

References

Ref 1	Inhibition of Bcl-xL by ABT-737 enhances chemotherapy sensitivity in neurofibromatosis type 1-associated malignant peripheral nerve sheath tumor cells .Int J Mol Med. 2012 Aug;30(2):443-50. doi: 10.3892/ijmm.2012.1013. Epub 2012 May 29. 10.3892/ijmm.2012.1013
Ref 2	Combined Cyclin-Dependent Kinase Inhibition Overcomes MAPK/Extracellular Signal-Regulated Kinase Kinase Inhibitor Resistance in Plexiform Neurofibroma of Neurofibromatosis Type I .J Invest Dermatol. 2022 Mar;142(3 Pt A):613-623.e7. doi: 10.1016/j.jid.2021.07.164. Epub 2021 Sep 15. 10.1016/j.jid.2021.07.164