AUTHOR=Al-Odat Omar S. , von Suskil Max , Chitren Robert J. , Elbezanti Weam O. , Srivastava Sandeep K. , Budak-Alpddogan Tulin , Jonnalagadda Subash C. , Aggarwal Bharat B. , Pandey Manoj TITLE=Mcl-1 Inhibition: Managing Malignancy in Multiple Myeloma JOURNAL=Frontiers in Pharmacology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.699629 DOI=10.3389/fphar.2021.699629 ISSN=1663-9812 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.