PT  - JOURNAL ARTICLE
AU  - JOSHUA E. LOGAN
AU  - NIKAYEH MOSTOFIZADEH
AU  - AMRITA J. DESAI
AU  - ERIKA VON EUW
AU  - DYLAN CONKLIN
AU  - VEERAUO KONKANKIT
AU  - HABIB HAMIDI
AU  - MARK ECKARDT
AU  - LEE ANDERSON
AU  - HSIAO-WANG CHEN
AU  - CHARLES GINTHER
AU  - EILEEN TASCHEREAU
AU  - PETER H. BUI
AU  - JAMES G. CHRISTENSEN
AU  - ARIE S. BELLDEGRUN
AU  - DENNIS J. SLAMON
AU  - FAIROOZ F. KABBINAVAR
TI  - 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
DP  - 2013 Aug 01
TA  - Anticancer Research
PG  - 2997--3004
VI  - 33
IP  - 8
4099  - http://ar.iiarjournals.org/content/33/8/2997.short
4100  - http://ar.iiarjournals.org/content/33/8/2997.full
SO  - Anticancer Res2013 Aug 01; 33
AB  - Background: 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. Materials and Methods: 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. Results: 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). Conclusion: PD-0332991 has antiproliferative activity in RCC cell lines, and molecular markers predict for sensitivity to this agent.