Targeting MCL-1 in hematologic malignancies: Rationale and progress
- Author(s)
- Wei, AH; Roberts, AW; Spencer, A; Rosenberg, AS; Siegel, D; Walter, RB; Caenepeel, S; Hughes, P; McIver, Z; Mezzi, K; Morrow, PK; Stein, A;
- Journal Title
- Blood Reviews
- Publication Type
- Journal epub ahead of print
- 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.
- Publisher
- EDP Sciences
- Research Division(s)
- Blood Cells And Blood Cancer
- PubMed ID
- 32204955
- Publisher's Version
- https://doi.org/10.1016/j.blre.2020.100672
- Open Access at Publisher's Site
https://doi.org/10.1016/j.blre.2020.100672- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2020-03-26 01:51:55
Last Modified: 2020-05-04 11:32:32