期刊
JOURNAL OF HEMATOLOGY & ONCOLOGY
卷 13, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s13045-020-01007-9
关键词
Myeloid cell leukemia 1; MCL-1; BCL-2; Dependency; Inhibitor; Apoptosis; Cancer; Leukemia; Myeloma; Lymphoma; Melanoma
资金
- Austrian Forum against Cancer
- Foundation Against Cancer
- Fonds National de la Recherche Scientifique (FNRS, Belgium)
- Fondation Veronique Cornet
- Fonds Speciaux de la Recherche (University of Liege)
- Belgian Foundation Against Cancer
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.
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