MCL-1 inhibitors, fast-lane development of a new class of anti-cancer agents

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.

Errataetall:

ErratumIn: J Hematol Oncol. 2021 Feb 17;14(1):31. - PMID 33596924

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:13

Enthalten in:

Journal of hematology & oncology - 13(2020), 1 vom: 11. Dez., Seite 173

Sprache:

Englisch

Beteiligte Personen:

Bolomsky, Arnold [VerfasserIn]
Vogler, Meike [VerfasserIn]
Köse, Murat Cem [VerfasserIn]
Heckman, Caroline A [VerfasserIn]
Ehx, Grégory [VerfasserIn]
Ludwig, Heinz [VerfasserIn]
Caers, Jo [VerfasserIn]

Links:

Volltext

Themen:

Antineoplastic Agents
Apoptosis
BCL-2
Cancer
Dependency
Inhibitor
Journal Article
Leukemia
Lymphoma
MCL-1
Melanoma
Myeloid Cell Leukemia Sequence 1 Protein
Myeloid cell leukemia 1
Myeloma
Research Support, Non-U.S. Gov't
Review
Small Molecule Libraries

Anmerkungen:

Date Completed 07.06.2021

Date Revised 07.06.2021

published: Electronic

ErratumIn: J Hematol Oncol. 2021 Feb 17;14(1):31. - PMID 33596924

Citation Status MEDLINE

doi:

10.1186/s13045-020-01007-9

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM318735865