• Joshua E Logan, Nikayeh Mostofizadeh, Amrita J Desai, Erika VON Euw, Dylan Conklin, Veerauo Konkankit, Habib Hamidi, Mark Eckardt, Lee Anderson, Hsiao-Wang Chen, Charles Ginther, Eileen Taschereau, Peter H Bui, James G Christensen, Arie S Belldegrun, Dennis J Slamon, and Fairooz F Kabbinavar.
• Institute of Urologic Oncology, Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, 924 Westwood Blvd., Suite 1050, Los Angeles, CA 90095, USA. Joshuaelogan@gmail.com
• Anticancer Res. 2013 Aug 1; 33 (8): 2997-3004.

BackgroundPD-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.Materials And MethodsHalf-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.ResultsIC50 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).ConclusionPD-0332991 has antiproliferative activity in RCC cell lines, and molecular markers predict for sensitivity to this agent.

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