CDK4/6 inhibitor resistance in prostate cancer

CDK4/6 kinase inhibitors have shown great promise in clinical trials in various cancer types and have recently entered clinical trial for advanced prostate cancer. Although patients are expected to respond well to this class of drugs, development of resistance in some patients is anticipated. To pre-empt this and study how prostate cancer may evade CDK4/6 inhibition, new resistance models were generated from LNCaP and LAPC4 prostate cancer cells cells by prolonged culturing in presence of 0.5uM palbociclib. RNA sequencing data was integrated with phospho-proteomics to unravel the molecular underpinnings of acquired resistance to palbociclib and resultant broad CDK4/6 inhibitor resistance. Overall design: Thirty total sample: three biological replicates of vehicle control and PD treated parental and Palbociclib (PD) resistant cells (PDR) that were generated from LAPC4 and LNCaP cells.

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de Leeuw R, McNair C, Schiewer MJ, Neupane NP, Brand LJ, Augello MA, Li Z, Cheng LC, Yoshida A, Courtney SM, Hazard ES, Hardiman G, Hussain MH, Diehl JA, Drake JM, Kelly WK, Knudsen KE