Developing targeted therapies to combine with venetoclax in acute myeloid leukemia (AML)

Marina Konopleva, MD, PhD, from the MD Anderson Cancer Centre, Houston, TX, discusses potential therapies to combine with venetoclax in acute myeloid leukemia (AML) at the International Symposium on Acute Leukemias (ISAL) 2017 in Munich, Germany. Venetoclax inhibitor BCL-2, with BCLXL and MCL-1 also part of the BCL-2 family. Particularly MCL-1 is highly expressed in AML, particularly in patients who progressed in venetoclax clinical trials. Dr Konopleva argues that this makes MCL-1 a good target in conjunction with venetoclax. Azacitidine inhibits MCL-1, but more targeted approaches include FLT3 inhibitors in FLT3-mutatnt AML, CDK9 inhibitors (as CDK9 controls MCL-1 transcription) and selective MCL-1 inhibitors developed by different companies. She concludes that it is well known that AML is a multiclonal disease, and that different clones express different proteins, therefore in future we should block both BCL-2 and MCL-1 to achieve the maximum response.

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