Journal article
Tailored first-line and second-line CDK4-targeting treatment combinations in mouse models of pancreatic cancer
A Chou, D Froio, AM Nagrial, A Parkin, KJ Murphy, VT Chin, D Wohl, A Steinmann, R Stark, A Drury, SN Walters, C Vennin, A Burgess, M Pinese, LA Chantrill, MJ Cowley, TJ Molloy, N Waddell, A Johns, SM Grimmond Show all
Gut | BMJ PUBLISHING GROUP | Published : 2018
Abstract
Objective Extensive molecular heterogeneity of pancreatic ductal adenocarcinoma (PDA), few effective therapies and high mortality make this disease a prime model for advancing development of tailored therapies. The p16-cyclin D-cyclin-dependent kinase 4/6-retinoblastoma (RB) protein (CDK4) pathway, regulator of cell proliferation, is deregulated in PDA. Our aim was to develop a novel personalised treatment strategy for PDA based on targeting CDK4. Design Sensitivity to potent CDK4/6 inhibitor PD-0332991 (palbociclib) was correlated to protein and genomic data in 19 primary patient-derived PDA lines to identify biomarkers of response. In vivo efficacy of PD-0332991 and combination therapies w..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
This work was supported by the National Health and Medical Research Council of Australia (NHMRC) Project Grants 1081312 and 1105640, Cancer Australia Project Grants 1060522 and 1100722 with fellowship support from Cancer Institute NSW, Australian Research Council and NHMRC, scholarship support from NHMRC and Sydney Catalyst and philanthropic support from the Avner Pancreatic Cancer Foundation, The Philip Hemstritch Fellowship in Pancreatic Cancer; Len Ainsworth Pancreatic Cancer Fellowship, Estate of the late RT Hall Cancer Gene Discovery and Validation Program and Norman Green Support Grant.