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Distinguished Guest Lecture

10 November 2016, 4:00 pm–5:00 pm

Andreas Strasser…

Professor Andreas Strasser, The Walter and Eliza Hall Institute of Medical Research, presents: Which pro-survival BCL-2 family member should be targeted for the treatment of which cancer?

Event Information

Location

UCL Pearson Lecture Theatre

Professor Strasser is an internationally recognised leader in cancer and immunology, with a particular focus on how defects in programmed cell death (apoptosis) cause cancer and affect the therapeutic responses of malignant tumour cells.

Hosted by: Professor Henning Walczak

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. Members of the BCL-2 family of proteins are key regulators of apoptosis and include proteins essential for cell survival and those required to initiate cell death. Studies with transgenic mice have shown that over-expression of BCL-2 or related pro-survival family proteins, such as BCL-XL or MCL-1, can promote tumorigenesis, particularly in conjunction with mutations that deregulate cell cycle control, such as deregulated c-MYC expression. It is, however, not known whether expression of pro-survival BCL-2 family members under endogenous control is required to maintain the survival of cells undergoing neoplastic transformation. We investigated the role of BCL-2 pro-survival proteins when expressed under endogenous control in the development of MYC-driven lymphoma and several other cancers. BCL-2 was found to be dispensable for the development of MYC-driven pre-B/B lymphoma. In contrast, loss of BCL-XL and even more remarkably, loss of only a single allele of Mcl-1 greatly impaired lymphoma development. Experiments with inducible knockout mice demonstrated that MCL-1 but not BCL-2 or BCL-XL is essential for the sustained survival and expansion of c-MYC-driven malignant pre-B/B lymphoma, AML driven by various oncogenes and T cell lymphoma driven by loss of p53. Remarkably, even loss of one allele of Mcl-1 greatly impaired lymphoma growth. Using inducible expression of guide RNAs that target different pro-survival BCL-2 family member we found that MCL-1 is also critical for the sustained growth of diverse human cancers, including MYC-driven Burkitt lymphoma. These observations indicate that even relatively weak targeting of MCL-1 may be an attractive strategy for the treatment of c-MYC-driven haematological malignancies and possibly also other cancers driven by different oncogenic lesions. We have therefor collaborated with the French pharma company Servier to develop MCL-1 inhibitory BH3 mimetic compounds for clinical trials of cancer patients. One of these compounds will be presented.

This lecture will be followed by a canapé reception at the Flaxman Gallery

Enquiries: Veronica Dominguez v.dominguez@ucl.ac.uk


Location

Pearson Lecture Theatre
UCL
Gower Street, 
London WC1E 6BT