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Targeting MCL-1 in hematologic malignancies: Rationale and progress
Blood Reviews ( IF 5.823 ) Pub Date : 2020-02-21 , DOI: 10.1016/j.blre.2020.100672
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

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.
更新日期:2020-02-21

 

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