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Ref Type Journal Article
PMID (23898052)
Authors Logan JE, Mostofizadeh N, Desai AJ, VON Euw E, Conklin D, Konkankit V, Hamidi H, Eckardt M, Anderson L, Chen HW, Ginther C, Taschereau E, Bui PH, Christensen JG, Belldegrun AS, Slamon DJ, Kabbinavar FF
Title PD-0332991, a potent and selective inhibitor of cyclin-dependent kinase 4/6, demonstrates inhibition of proliferation in renal cell carcinoma at nanomolar concentrations and molecular markers predict for sensitivity.
Abstract Text PD-0332991 is an inhibitor of cyclin-dependent kinases (CDK) 4 and 6, and was evaluated to determine its anti-proliferative effects in 25 renal cell carcinoma (RCC) cell lines.Half-maximal inhibitory concentrations (IC50) of PD-0332991 were determined with cell line proliferation assays, as were its effects on the cell cycle, apoptosis, and retinoblastoma (RB) phosphorylation. Molecular markers for response prediction, including p16, p15, cyclin D1 (CCND1), cyclin E1 (CCNE1), E2F transcription factor 1 (E2F1), RB, CDK4 and CDK6, were studied using array comparative genomic hybridization (CGH) and gene expression.IC50 values for PD-0332991 ranged from 25.0 nM to 700 nM, and the agent demonstrated G0/G1 cell-cycle arrest, induction of late apoptosis, and blockade of RB phosphorylation. Through genotype and expression data p16, p15 and E2F1 were identified as having significant association between loss and sensitivity to PD-0332991: p16 (p=0.021), p15 (p=0.047), and E2F1 (p=0.041).PD-0332991 has antiproliferative activity in RCC cell lines, and molecular markers predict for sensitivity to this agent.


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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 loss renal cell carcinoma sensitive Palbociclib Preclinical Actionable In a preclinical study, renal cell carcinoma cell lines with CDKN2A loss were sensitive to Palbociclib (PD-0332991) (PMID: 23898052). 23898052