Mcl-1 Inhibition: Managing Malignancy in Multiple Myeloma

Omar Al-Odat; Max von Suskil; Robert Chitren; Weam Elbezanti; Sandeep Srivastava; Tulin Budak-Alpddogan; Subash Jonnalagadda; Bharat Aggarwal; Manoj Pandey

doi:10.3389/fphar.2021.699629

Mcl-1 Inhibition: Managing Malignancy in Multiple Myeloma

Front Pharmacol. 2021 Jul 19:12:699629. doi: 10.3389/fphar.2021.699629. eCollection 2021.

Authors

Omar Al-Odat^{1

2}, Max von Suskil^{1

2}, Robert Chitren^{1

2}, Weam Elbezanti^{1

3}, Sandeep Srivastava⁴, Tulin Budak-Alpddogan³, Subash Jonnalagadda², Bharat Aggarwal⁵, Manoj Pandey¹

Affiliations

¹ Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ, United States.
² Department of Chemistry and Biochemistry, Rowan University, Glassboro, NJ, United States.
³ Department of Hematology, Cooper Health University, Camden, NJ, United States.
⁴ Department of Biosciences, Manipal University Jaipur, Jaipur, India.
⁵ Inflammation Research Center, San Diego, CA, United States.

Abstract

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.

Keywords: Bcl-2 homology 3 mimetics; Mcl-1; apoptosis; drug resistant; multiple myeloma.

Publication types

Review