TY - JOUR AU - Bolomsky, Arnold AU - Vogler, Meike AU - Köse, Murat Cem AU - Heckman, Caroline A. AU - Ehx, Grégory AU - Ludwig, Heinz AU - Caers, Jo PY - 2020 DA - 2020/12/11 TI - MCL-1 inhibitors, fast-lane development of a new class of anti-cancer agents JO - Journal of Hematology & Oncology SP - 173 VL - 13 IS - 1 AB - 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. SN - 1756-8722 UR - https://doi.org/10.1186/s13045-020-01007-9 DO - 10.1186/s13045-020-01007-9 ID - Bolomsky2020 ER -