Success in myeloma treatment in recent years has been built on a platform of immuno-modulatory drugs, proteasome inhibitors and more recently monoclonal antibodies targeting proteins expressed on myeloma cells. While effective, the repertoire of available agents is limited, and therapeutic resistance frequently arises. Targeting different aspects of myeloma biology may be an attractive way to increase our therapeutic armamentarium. In this regard, abnormalities in the cell death pathway (apoptosis) are common in B cell malignancies including multiple myeloma, and this is an area of cancer biology for which there is much interest in drug development. Targeting this pathway in myeloma patients has started in clinical trials.
Dr. Simone Fulda will describe the apoptosis pathway and machinery and discuss the mechanism by which this pathway is deregulated in myeloma. Novel opportunities to target the apoptosis pathway will also be discussed. How the pathway interacts with other important deregulated pathways in myeloma and how they can become an Achilles heel in myeloma where myeloma cells become dependent and therefore sensitive to the inhibition of the pathway will be discussed.
Dr. Martine Amiot will discuss the merits of targeting BCL2 proteins in myeloma. Both pre-clinical and clinical data will be critically evaluated. Different ways of stratifying patients for BCL2 inhibition will also be discussed. This is particularly relevant as these compounds are new the clinic and the ability to stratify and select patients will be key. BCL2 inhibition appears to benefit t(11;14) patients the most. Underlying reasons for this and how this can be further exploited will also be discussed.
Dr. Karin Vanderkerken will discuss the development of MCL1 inhibitors in myeloma and will present insights from pre-clinical studies and early results from clinical trials. Of note, potential rationale combinations and biomarkers arising from pre-clinical studies will be discuss and strategies for future us of these compounds in myeloma in the setting of current therapeutic armamentarium will be explored.
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