Cargando…
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 malignanci...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731749/ https://www.ncbi.nlm.nih.gov/pubmed/33308268 http://dx.doi.org/10.1186/s13045-020-01007-9 |
_version_ | 1783621963037540352 |
---|---|
author | Bolomsky, Arnold Vogler, Meike Köse, Murat Cem Heckman, Caroline A. Ehx, Grégory Ludwig, Heinz Caers, Jo |
author_facet | Bolomsky, Arnold Vogler, Meike Köse, Murat Cem Heckman, Caroline A. Ehx, Grégory Ludwig, Heinz Caers, Jo |
author_sort | Bolomsky, Arnold |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7731749 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-77317492020-12-15 MCL-1 inhibitors, fast-lane development of a new class of anti-cancer agents Bolomsky, Arnold Vogler, Meike Köse, Murat Cem Heckman, Caroline A. Ehx, Grégory Ludwig, Heinz Caers, Jo J Hematol Oncol Review 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. BioMed Central 2020-12-11 /pmc/articles/PMC7731749/ /pubmed/33308268 http://dx.doi.org/10.1186/s13045-020-01007-9 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Review Bolomsky, Arnold Vogler, Meike Köse, Murat Cem Heckman, Caroline A. Ehx, Grégory Ludwig, Heinz Caers, Jo MCL-1 inhibitors, fast-lane development of a new class of anti-cancer agents |
title | MCL-1 inhibitors, fast-lane development of a new class of anti-cancer agents |
title_full | MCL-1 inhibitors, fast-lane development of a new class of anti-cancer agents |
title_fullStr | MCL-1 inhibitors, fast-lane development of a new class of anti-cancer agents |
title_full_unstemmed | MCL-1 inhibitors, fast-lane development of a new class of anti-cancer agents |
title_short | MCL-1 inhibitors, fast-lane development of a new class of anti-cancer agents |
title_sort | mcl-1 inhibitors, fast-lane development of a new class of anti-cancer agents |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731749/ https://www.ncbi.nlm.nih.gov/pubmed/33308268 http://dx.doi.org/10.1186/s13045-020-01007-9 |
work_keys_str_mv | AT bolomskyarnold mcl1inhibitorsfastlanedevelopmentofanewclassofanticanceragents AT voglermeike mcl1inhibitorsfastlanedevelopmentofanewclassofanticanceragents AT kosemuratcem mcl1inhibitorsfastlanedevelopmentofanewclassofanticanceragents AT heckmancarolinea mcl1inhibitorsfastlanedevelopmentofanewclassofanticanceragents AT ehxgregory mcl1inhibitorsfastlanedevelopmentofanewclassofanticanceragents AT ludwigheinz mcl1inhibitorsfastlanedevelopmentofanewclassofanticanceragents AT caersjo mcl1inhibitorsfastlanedevelopmentofanewclassofanticanceragents |