Journal article
Resistance to CDK2 inhibitors is associated with selection of polyploid cells in CCNE1-amplified ovarian cancer
D Etemadmoghadam, G Au-Yeung, M Wall, C Mitchell, M Kansara, E Loehrer, C Batzios, J George, S Ftouni, BA Weir, S Carter, I Gresshoff, L Mileshkin, D Rischin, WC Hahn, PM Waring, G Getz, C Cullinane, LJ Campbell, DD Bowtell
Clinical Cancer Research | AMER ASSOC CANCER RESEARCH | Published : 2013
Abstract
Purpose: Amplification of cyclin E1 (CCNE1) is associated with poor outcome in breast, lung, and other solid cancers, and is the most prominent structural variant associated with primary treatment failure in highgrade serous ovarian cancer (HGSC). We have previously shown that CCNE1-amplified tumors show amplicon-dependent sensitivity to CCNE1 suppression. Here, we explore targeting CDK2 as a novel therapeutic strategy in CCNE1-amplified cancers and mechanisms of resistance. Experimental Design: We examined the effect of CDK2 suppression using RNA interference and smallmolecule inhibitors in SK-OV-3, OVCAR-4, and OVCAR-3 ovarian cancer cell lines. To identify mechanisms of resistance, we der..
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Funding Acknowledgements
This work was funded by a National Health and Medical Research Council (NHMRC) project grant (APP 1042358).