Reference Detail

Ref Type

Journal Article

PMID

(21871868)

Authors

Katsumi Y, Iehara T, Miyachi M, Yagyu S, Tsubai-Shimizu S, Kikuchi K, Tamura S, Kuwahara Y, Tsuchiya K, Kuroda H, Sugimoto T, Houghton PJ, Hosoi H

Title

Sensitivity of malignant rhabdoid tumor cell lines to PD 0332991 is inversely correlated with p16 expression.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Biochemical and biophysical research communications	413	1	2011 Sep 16	62-8	Biochem Biophys Res Commun

URL

Abstract Text

Malignant rhabdoid tumor (MRT) is a rare and highly aggressive neoplasm of young children. MRT is characterized by inactivation of integrase interactor 1 (INI1). Cyclin-dependent kinase 4 (CDK4), which acts downstream of INI1, is required for the proliferation of MRT cells. Here we investigated the effects of PD 0332991 (PD), a potent inhibitor of CDK4, against five human MRT cell lines (MP-MRT-AN, KP-MRT-RY, G401, KP-MRT-NS, KP-MRT-YM). In all of the cell lines except KP-MRT-YM, PD inhibited cell proliferation >50%, (IC(50) values 0.01 to 0.6 μM) by WST-8 assay, and induced G1-phase cell cycle arrest, as shown by flow cytometry and BrdU incorporation assay. The sensitivity of the MRT cell lines to PD was inversely correlated with p16 expression (r=0.951). KP-MRT-YM cells overexpress p16 and were resistant to the growth inhibitory effect of PD. Small interfering RNA against p16 significantly increased the sensitivity of KP-MRT-YM cells to PD (p<0.05). These results suggest that p16 expression in MRT could be used to predict its sensitivity to PD. PD may be an attractive agent for patients with MRT whose tumors express low levels of p16.

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Molecular Profile	Treatment Approach
SMARCB1 loss	CDK4/6 Inhibitor
SMARCB1 T72Qfs*13	CDK4/6 Inhibitor
SMARCB1 E31V	CDK4/6 Inhibitor
SMARCB1 T72Nfs*4	CDK4/6 Inhibitor
SMARCB1 del	CDK4/6 Inhibitor
SMARCB1 R53*	CDK4/6 Inhibitor
SMARCB1 T118Pfs*25	CDK4/6 Inhibitor
SMARCB1 Q18*	CDK4/6 Inhibitor
SMARCB1 L166Pfs*4	CDK4/6 Inhibitor

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
CDKN2A over exp SMARCB1 neg	rhabdoid cancer	decreased response	Palbociclib	Preclinical	Actionable	In a preclinical study, CDKN2A (p16) over expression was associated with decreased sensitivity to Ibrance (palbociclib) in a SMARCB1-negative malignant rhabdoid tumor cell line in culture (PMID: 21871868).	21871868
SMARCB1 negative	rhabdoid cancer	sensitive	Palbociclib	Preclinical	Actionable	In a preclinical study, Ibrance (palbociclib) inhibited growth of SMARCB1-negative malignant rhabdoid tumor cell lines in culture, and sensitivity was associated with low levels of p16 expression (PMID: 21871868).	21871868