Cargando…

Myeloid cell leukemia-1: a formidable barrier to anticancer therapeutics and the quest of targeting it

The antiapoptotic B cell lymphoma-2 (Bcl-2) family members are apical regulators of the intrinsic pathway of apoptosis that orchestrate mitochondrial outer membrane permeabilization (MOMP) through interactions with their proapoptotic counterparts. Overexpression of antiapoptotic Bcl-2 family protein...

Descripción completa

Detalles Bibliográficos
Autores principales: Sulkshane, Prasad, Teni, Tanuja
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Open Exploration 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9400788/
https://www.ncbi.nlm.nih.gov/pubmed/36045907
http://dx.doi.org/10.37349/etat.2022.00083
_version_ 1784772818882265088
author Sulkshane, Prasad
Teni, Tanuja
author_facet Sulkshane, Prasad
Teni, Tanuja
author_sort Sulkshane, Prasad
collection PubMed
description The antiapoptotic B cell lymphoma-2 (Bcl-2) family members are apical regulators of the intrinsic pathway of apoptosis that orchestrate mitochondrial outer membrane permeabilization (MOMP) through interactions with their proapoptotic counterparts. Overexpression of antiapoptotic Bcl-2 family proteins has been linked to therapy resistance and poor prognosis in diverse cancers. Among the antiapoptotic Bcl-2 family members, predominant overexpression of the prosurvival myeloid cell leukemia-1 (Mcl-1) has been reported in a myriad of hematological malignancies and solid tumors, contributing to therapy resistance and poor outcomes, thus making it a potential druggable target. The unique structure of Mcl-1 and its complex regulatory mechanism makes it an adaptive prosurvival switch that ensures tumor cell survival despite therapeutic intervention. This review focusses on diverse mechanisms adopted by tumor cells to maintain sustained elevated levels of Mcl-1 and how high Mcl-1 levels contribute to resistance in conventional as well as targeted therapies. Moreover, recent developments in the Mcl-1-targeted therapeutics and the underlying challenges and considerations in designing novel Mcl-1 inhibitors are also discussed.
format Online
Article
Text
id pubmed-9400788
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Open Exploration
record_format MEDLINE/PubMed
spelling pubmed-94007882022-08-30 Myeloid cell leukemia-1: a formidable barrier to anticancer therapeutics and the quest of targeting it Sulkshane, Prasad Teni, Tanuja Explor Target Antitumor Ther Review The antiapoptotic B cell lymphoma-2 (Bcl-2) family members are apical regulators of the intrinsic pathway of apoptosis that orchestrate mitochondrial outer membrane permeabilization (MOMP) through interactions with their proapoptotic counterparts. Overexpression of antiapoptotic Bcl-2 family proteins has been linked to therapy resistance and poor prognosis in diverse cancers. Among the antiapoptotic Bcl-2 family members, predominant overexpression of the prosurvival myeloid cell leukemia-1 (Mcl-1) has been reported in a myriad of hematological malignancies and solid tumors, contributing to therapy resistance and poor outcomes, thus making it a potential druggable target. The unique structure of Mcl-1 and its complex regulatory mechanism makes it an adaptive prosurvival switch that ensures tumor cell survival despite therapeutic intervention. This review focusses on diverse mechanisms adopted by tumor cells to maintain sustained elevated levels of Mcl-1 and how high Mcl-1 levels contribute to resistance in conventional as well as targeted therapies. Moreover, recent developments in the Mcl-1-targeted therapeutics and the underlying challenges and considerations in designing novel Mcl-1 inhibitors are also discussed. Open Exploration 2022 2022-05-24 /pmc/articles/PMC9400788/ /pubmed/36045907 http://dx.doi.org/10.37349/etat.2022.00083 Text en © The Author(s) 2022. https://creativecommons.org/licenses/by/4.0/This is an Open Access article licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Review
Sulkshane, Prasad
Teni, Tanuja
Myeloid cell leukemia-1: a formidable barrier to anticancer therapeutics and the quest of targeting it
title Myeloid cell leukemia-1: a formidable barrier to anticancer therapeutics and the quest of targeting it
title_full Myeloid cell leukemia-1: a formidable barrier to anticancer therapeutics and the quest of targeting it
title_fullStr Myeloid cell leukemia-1: a formidable barrier to anticancer therapeutics and the quest of targeting it
title_full_unstemmed Myeloid cell leukemia-1: a formidable barrier to anticancer therapeutics and the quest of targeting it
title_short Myeloid cell leukemia-1: a formidable barrier to anticancer therapeutics and the quest of targeting it
title_sort myeloid cell leukemia-1: a formidable barrier to anticancer therapeutics and the quest of targeting it
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9400788/
https://www.ncbi.nlm.nih.gov/pubmed/36045907
http://dx.doi.org/10.37349/etat.2022.00083
work_keys_str_mv AT sulkshaneprasad myeloidcellleukemia1aformidablebarriertoanticancertherapeuticsandthequestoftargetingit
AT tenitanuja myeloidcellleukemia1aformidablebarriertoanticancertherapeuticsandthequestoftargetingit