Targeting MCL-1 in hematologic malignancies: Rationale and progress. (November 2020)

• Record Type: Journal Article
• Authors: Wei, Andrew H.; Roberts, Andrew W.; Spencer, Andrew; Rosenberg, Aaron Seth; Siegel, David; Walter, Roland B.; Caenepeel, Sean; Hughes, Paul; McIver, Zach; Mezzi, Khalid; Morrow, Phuong Khanh; Stein, Anthony
• Is Part Of: Blood reviews. Volume 44(2020)
• Publication Date: 2020-11
• Subjects: MCL-1 inhibitor -- Multiple myeloma -- Acute myeloid leukemia -- Non-Hodgkin lymphoma -- BH3-mimetic; Hematology -- Periodicals; Hematology -- Periodicals; Hématologie -- Périodiques; Hematology; Electronic journals; Periodicals; 616.15
• DOI: 10.1016/j.blre.2020.100672
• Languages: English
• ISSNs: 0268-960X

Abstract

Abstract: 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.