Journal of Hematology & Oncology | |
MCL-1 inhibitors, fast-lane development of a new class of anti-cancer agents | |
Jo Caers1  Meike Vogler1  Grégory Ehx2  Murat Cem Köse2  Caroline A. Heckman3  Arnold Bolomsky4  Heinz Ludwig4  | |
[1] Department of Clinical Hematology, GIGA-I3, University of Liège, CHU De Liège, 35, Dom Univ Sart Tilman B, 4000, Liège, Belgium;Institute for Experimental Cancer Research in Pediatrics, Goethe-University, Frankfurt, Germany;Institute for Molecular Medicine Finland—FIMM, HiLIFE—Helsinki Institute of Life Science, iCAN Digital Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland;Wilhelminen Cancer Research Institute, Wilhelminenspital, Vienna, Austria; | |
关键词: Myeloid cell leukemia 1; MCL-1; BCL-2; Dependency; Inhibitor; Apoptosis; Cancer; Leukemia; Myeloma; Lymphoma; Melanoma; | |
DOI : 10.1186/s13045-020-01007-9 | |
来源: Springer | |
【 摘 要 】
Cell death escape is one of the most prominent features of tumor cells and closely linked to the dysregulation of members of the Bcl-2 family of proteins. Among those, the anti-apoptotic family member myeloid cell leukemia-1 (MCL-1) acts as a master regulator of apoptosis in various human malignancies. Irrespective of its unfavorable structure profile, independent research efforts recently led to the generation of highly potent MCL-1 inhibitors that are currently evaluated in clinical trials. This offers new perspectives to target a so far undruggable cancer cell dependency. However, a detailed understanding about the tumor and tissue type specific implications of MCL-1 are a prerequisite for the optimal (i.e., precision medicine guided) use of this novel drug class. In this review, we summarize the major functions of MCL-1 with a special focus on cancer, provide insights into its different roles in solid vs. hematological tumors and give an update about the (pre)clinical development program of state-of-the-art MCL-1 targeting compounds. We aim to raise the awareness about the heterogeneous role of MCL-1 as drug target between, but also within tumor entities and to highlight the importance of rationale treatment decisions on a case by case basis.
【 授权许可】
CC BY
【 预 览 】
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RO202106294480727ZK.pdf | 1617KB | download |