Journal article
Deciphering the molecular events necessary for synergistic tumor cell apoptosis mediated by the histone deacetylase inhibitor vorinostat and the BH3 mimetic ABT-737
AP Wiegmans, AE Alsop, M Bots, LA Cluse, SP Williams, KM Banks, R Ralli, CL Scott, A Frenzel, A Villunger, RW Johnstone
Cancer Research | Published : 2011
Abstract
The concept of personalized anticancer therapy is based on the use of targeted therapeutics through in-depth knowledge of the molecular mechanisms of action of these agents when used alone and in combination. We have identified the apoptotic proteins and pathways necessary for synergistic tumor cell apoptosis and in vivo antitumor responses seen when the HDAC inhibitor vorinostat is combined with the BH3-mimetic ABT-737 in lymphomas overexpressing Bcl-2. Vorinostat "primes" tumors overexpressing Bcl-2 for rapid ABT-737-mediated apoptosis by inducing expression of the BH3-only gene bmf. Moreover, these synergistic effects of vorinostat/ABT-737 were blunted in cells with an inactive p53 pathwa..
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Awarded by AICR
Funding Acknowledgements
R.W. Johnstone is a Principal Research Fellow of the National Health and Medical Research Council of Australia (NHMRC) and supported by NHMRC Program and Project Grants, the Susan G. Komen Breast Cancer Foundation, the Prostate Cancer Foundation of Australia, Cancer Council Victoria, Victorian Breast Cancer Research Consortium, and the Australian Rotary Health Foundation. A. Villunger is supported by the AICR (grant no. 06-440) and the Austrian Science Fund (FWF). R.W. Johnstone received a collaborative research grant from Merck and Co. for research involving vorinostat.