Cargando…
Clinical Translation of Combined MAPK and Autophagy Inhibition in RAS Mutant Cancer
RAS (rat sarcoma virus) mutant cancers remain difficult to treat despite the advances in targeted therapy and immunotherapy. Targeted therapies against the components of mitogen-activated protein kinase (MAPK) pathways, including RAS, RAF, MEK, and ERK, have demonstrated activity in BRAF mutant and,...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8623813/ https://www.ncbi.nlm.nih.gov/pubmed/34830283 http://dx.doi.org/10.3390/ijms222212402 |
_version_ | 1784606022306889728 |
---|---|
author | Lee, Jennifer J. Jain, Vaibhav Amaravadi, Ravi K. |
author_facet | Lee, Jennifer J. Jain, Vaibhav Amaravadi, Ravi K. |
author_sort | Lee, Jennifer J. |
collection | PubMed |
description | RAS (rat sarcoma virus) mutant cancers remain difficult to treat despite the advances in targeted therapy and immunotherapy. Targeted therapies against the components of mitogen-activated protein kinase (MAPK) pathways, including RAS, RAF, MEK, and ERK, have demonstrated activity in BRAF mutant and, in limited cases, RAS mutant cancer. RAS mutant cancers have been found to activate adaptive resistance mechanisms such as autophagy during MAPK inhibition. Here, we review the recent clinically relevant advances in the development of the MAPK pathway and autophagy inhibitors and focus on their application to RAS mutant cancers. We provide analysis of the preclinical rationale for combining the MAPK pathway and autophagy and highlight the most recent clinical trials that have been launched to capitalize on this potentially synthetic lethal approach to cancer therapy. |
format | Online Article Text |
id | pubmed-8623813 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-86238132021-11-27 Clinical Translation of Combined MAPK and Autophagy Inhibition in RAS Mutant Cancer Lee, Jennifer J. Jain, Vaibhav Amaravadi, Ravi K. Int J Mol Sci Review RAS (rat sarcoma virus) mutant cancers remain difficult to treat despite the advances in targeted therapy and immunotherapy. Targeted therapies against the components of mitogen-activated protein kinase (MAPK) pathways, including RAS, RAF, MEK, and ERK, have demonstrated activity in BRAF mutant and, in limited cases, RAS mutant cancer. RAS mutant cancers have been found to activate adaptive resistance mechanisms such as autophagy during MAPK inhibition. Here, we review the recent clinically relevant advances in the development of the MAPK pathway and autophagy inhibitors and focus on their application to RAS mutant cancers. We provide analysis of the preclinical rationale for combining the MAPK pathway and autophagy and highlight the most recent clinical trials that have been launched to capitalize on this potentially synthetic lethal approach to cancer therapy. MDPI 2021-11-17 /pmc/articles/PMC8623813/ /pubmed/34830283 http://dx.doi.org/10.3390/ijms222212402 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Lee, Jennifer J. Jain, Vaibhav Amaravadi, Ravi K. Clinical Translation of Combined MAPK and Autophagy Inhibition in RAS Mutant Cancer |
title | Clinical Translation of Combined MAPK and Autophagy Inhibition in RAS Mutant Cancer |
title_full | Clinical Translation of Combined MAPK and Autophagy Inhibition in RAS Mutant Cancer |
title_fullStr | Clinical Translation of Combined MAPK and Autophagy Inhibition in RAS Mutant Cancer |
title_full_unstemmed | Clinical Translation of Combined MAPK and Autophagy Inhibition in RAS Mutant Cancer |
title_short | Clinical Translation of Combined MAPK and Autophagy Inhibition in RAS Mutant Cancer |
title_sort | clinical translation of combined mapk and autophagy inhibition in ras mutant cancer |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8623813/ https://www.ncbi.nlm.nih.gov/pubmed/34830283 http://dx.doi.org/10.3390/ijms222212402 |
work_keys_str_mv | AT leejenniferj clinicaltranslationofcombinedmapkandautophagyinhibitioninrasmutantcancer AT jainvaibhav clinicaltranslationofcombinedmapkandautophagyinhibitioninrasmutantcancer AT amaravadiravik clinicaltranslationofcombinedmapkandautophagyinhibitioninrasmutantcancer |