Targeting MCL-1 in hematologic malignancies: Rationale and progress.

Andrew H Wei, Andrew W Roberts, Andrew Spencer, Aaron Seth Rosenberg, David Siegel, Roland B Walter, Sean Caenepeel, Paul Hughes, Zach McIver, Khalid Mezzi, Phuong Khanh Morrow, Anthony Stein

Blood reviews 2020 Nov

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Myeloid cell leukemia sequence 1 (MCL-1) is an antiapoptotic protein that plays a key role in promoting cell survival in multiple myeloma (MM), acute myeloid leukemia (AML), and non-Hodgkin lymphoma (NHL). Overexpression of MCL-1 is associated with treatment resistance and poor prognosis; thus, MCL-1 inhibitors are rational therapeutic options for malignancies depending on MCL-1. Several MCL-1 inhibitors have entered clinical trials, including AZD5991, S64315, AMG 176, and AMG 397. A key area of investigation is whether MCL-1 inhibitors will complement the activity of BCL-2 inhibitors, such as venetoclax, and synergistically enhance anti-tumor efficacy when given in combination with other anti-cancer drugs. Another important question is whether a safe therapeutic window can be found for this new class of inhibitors. In summary, inhibition of MCL-1 shows potential as a treatment for hematologic malignancies and clinical evaluation of MCL-1 inhibitors is currently underway. Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Citation

Andrew H Wei, Andrew W Roberts, Andrew Spencer, Aaron Seth Rosenberg, David Siegel, Roland B Walter, Sean Caenepeel, Paul Hughes, Zach McIver, Khalid Mezzi, Phuong Khanh Morrow, Anthony Stein. Targeting MCL-1 in hematologic malignancies: Rationale and progress. Blood reviews. 2020 Nov;44:100672