Abstract IA31: Harnessing death for life.

Impaired apoptosis is a critical step in the development of cancer and a major impediment to effective therapy. Bcl-2, the oncoprotein activated by chromosome translocation in human follicular lymphoma, inhibits cells from undergoing apoptosis in response to many cytotoxic agents. Several close relatives (Bcl-xL, Bcl-w, Mcl-1 and A1) are also anti-apoptotic but others (Bax and Bak) are instead pro-apoptotic, despite strong sequence and structural homology. More distant pro-apoptotic family members, the ‘BH3-only proteins’, are largely unrelated, apart from the signature BH3 (Bcl-2 homology region 3) domain that is essential for their killing function. Using mouse models, we have shown that over-expression of Bcl-2 or Mcl-1, or loss of the BH3-only protein Bim, exacerbates a variety of lymphoid and myeloid neoplasias. Our recent preclinical studies suggest that small molecules mimicking BH3 domains will be effective cancer therapeutics. Citation Format: Cassandra Vandenberg, Suzanne Cory, Rebecca Bilardi, Natasha Anstee, Phillipe Bouillet, Andreas Strasser. Harnessing death for life. [abstract]. In: Proceedings of the AACR Special Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(17 Suppl):Abstract nr IA31.