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

Authors :: Wei AH
Roberts AW
Spencer A
Rosenberg AS
Siegel D
Walter RB
Caenepeel S
Hughes P
McIver Z
Mezzi K
Morrow PK
Stein A
Source :: Blood reviews [Blood Rev] 2020 Nov; Vol. 44, pp. 100672. Date of Electronic Publication: 2020 Feb 21.
Publication Year :: 2020
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.<br /> (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)