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

Research output: Contribution to journalReview articlepeer-review

7 Scopus citations

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.

Original languageEnglish (US)
Article number100672
JournalBlood Reviews
DOIs
StateAccepted/In press - Jan 1 2020

Keywords

  • Acute myeloid leukemia
  • BH3-mimetic
  • MCL-1 inhibitor
  • Multiple myeloma
  • Non-Hodgkin lymphoma

ASJC Scopus subject areas

  • Hematology
  • Oncology

Fingerprint Dive into the research topics of 'Targeting MCL-1 in hematologic malignancies: Rationale and progress'. Together they form a unique fingerprint.

Cite this