Frontiers in Pharmacology (Jul 2021)

Mcl-1 Inhibition: Managing Malignancy in Multiple Myeloma

  • Omar S. Al-Odat,
  • Omar S. Al-Odat,
  • Max von Suskil,
  • Max von Suskil,
  • Robert J. Chitren,
  • Robert J. Chitren,
  • Weam O. Elbezanti,
  • Weam O. Elbezanti,
  • Sandeep K. Srivastava,
  • Tulin Budak-Alpddogan,
  • Subash C. Jonnalagadda,
  • Bharat B. Aggarwal,
  • Manoj Pandey

DOI
https://doi.org/10.3389/fphar.2021.699629
Journal volume & issue
Vol. 12

Abstract

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Multiple myeloma (MM) is a plasma cells neoplasm. The overexpression of Bcl-2 family proteins, particularly myeloid cell leukemia 1 (Mcl-1), plays a critical role in the pathogenesis of MM. The overexpression of Mcl-1 is associated with drug resistance and overall poor prognosis of MM. Thus, inhibition of the Mcl-1 protein considered as a therapeutic strategy to kill the myeloma cells. Over the last decade, the development of selective Mcl-1 inhibitors has seen remarkable advancement. This review presents the critical role of Mcl-1 in the progression of MM, the most prominent BH3 mimetic and semi-BH3 mimetic that selectively inhibit Mcl-1, and could be used as single agent or combined with existing therapies.

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