CSCB Seminar Series : "Towards targeting MCL-1 for therapy." by Dr. Andreas Strasser
Amphitheatre, Level 2
Duke-NUS Medical School
8 College Road, S169857
Andreas Strasser MSc, PhD
Professor, Alan Harris Chair in Experimental Cancer Biology
The Walter & Eliza Hall Institute of Medical Research
Impaired apoptosis is considered one of the prerequisites for the development of most, if not all, cancers, but the mechanisms that guarantee the sustained survival of most cancer cells remain unknown. We examined the roles of individual pro-survival BCL-2 family members (when expressed under endogenous control) in lymphoma development. BCL-2 was found to be dispensable for the development of lymphoma. In contrast, loss of BCL-XL and even more remarkably, loss of a single allele of Mcl-1 greatly impaired lymphoma development in Eµ-Myc mice. Experiments with inducible knockout mice demonstrated that MCL-1 is essential for the sustained survival and expansion of MYC-driven malignant pore-B/B lymphoma. In collaboration with the pharma company Servier we have been testing S63845, a novel potent and selective inhibitor of MCL-1. S63845 was well tolerated in mice and could potently kill many human multiple myeloma, acute myeloid leukaemia and several other haematological and even solid cancer cell lines as single agent. These results reveal that the targeting of MCL-1 could be a promising strategy for the treatment of diverse cancers.
Andreas Strasser is noted for his studies on the control of programmed cell death, apoptosis. He demonstrated that impaired apoptosis can provoke cancer and autoimmune diseases and can render tumour cells refractory to many anti-cancer therapeutics. He established that mammals possess two distinct pathways to apoptosis, one triggered by ligation of cell surface "death receptors" and the other involving mitochondria being regulated by the BCL-2 protein family. He demonstrated that BH3-only proteins are critical initiators of apoptosis. These discoveries have major biological implications and have fuelled the development of novel therapeutic strategies for cancer and autoimmune diseases. The BCL-2 inhibitor, ABT-199 (venetoclax), co-developed by his Institute with Genentech and AbbVie was recently approved by the US FDA for treatment of relapsed/refractory chronic lymphocytic leukaemia and an MCL-1 inhibitor (co-developed with Servier) is destined to enter clinical trials in 2017.
Dr. FU Naiyang, PhD
Programme in Cancer & Stem Cell Biology
Duke-NUS Medical School
Amanda Chan (Tel: 6601 5700)