Clinical Translation of Combined MAPK and Autophagy Inhibition in <i>RAS</i> Mutant Cancer

Clinical Translation of Combined MAPK and Autophagy Inhibition in <i>RAS</i> Mutant Cancer

<i>RAS</i> (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 <i>RAS</i>, RAF, MEK, and ERK, have dem...

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Autores principales: Jennifer J. Lee, Vaibhav Jain, Ravi K. Amaravadi
Formato: article
Lenguaje:EN
Publicado: MDPI AG 2021
Materias:
<i>RAS</i>
autophagy
lysosome
Biology (General)
QH301-705.5
Chemistry
QD1-999
Acceso en línea:https://doaj.org/article/24c45a2ea6b847d1986090179b718cf8
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spelling oai:doaj.org-article:24c45a2ea6b847d1986090179b718cf82021-11-25T17:56:19ZClinical Translation of Combined MAPK and Autophagy Inhibition in <i>RAS</i> Mutant Cancer10.3390/ijms2222124021422-00671661-6596https://doaj.org/article/24c45a2ea6b847d1986090179b718cf82021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12402https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067<i>RAS</i> (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 <i>RAS</i>, RAF, MEK, and ERK, have demonstrated activity in <i>BRAF</i> mutant and, in limited cases, <i>RAS</i> mutant cancer. <i>RAS</i> 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 <i>RAS</i> 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.Jennifer J. LeeVaibhav JainRavi K. AmaravadiMDPI AGarticle<i>RAS</i>autophagylysosomeBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12402, p 12402 (2021)
institution DOAJ
collection DOAJ
language EN
topic <i>RAS</i>
autophagy
lysosome
Biology (General)
QH301-705.5
Chemistry
QD1-999
spellingShingle <i>RAS</i>
autophagy
lysosome
Biology (General)
QH301-705.5
Chemistry
QD1-999
Jennifer J. Lee
Vaibhav Jain
Ravi K. Amaravadi
Clinical Translation of Combined MAPK and Autophagy Inhibition in <i>RAS</i> Mutant Cancer
description <i>RAS</i> (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 <i>RAS</i>, RAF, MEK, and ERK, have demonstrated activity in <i>BRAF</i> mutant and, in limited cases, <i>RAS</i> mutant cancer. <i>RAS</i> 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 <i>RAS</i> 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 article
author Jennifer J. Lee
Vaibhav Jain
Ravi K. Amaravadi
author_facet Jennifer J. Lee
Vaibhav Jain
Ravi K. Amaravadi
author_sort Jennifer J. Lee
title Clinical Translation of Combined MAPK and Autophagy Inhibition in <i>RAS</i> Mutant Cancer
title_short Clinical Translation of Combined MAPK and Autophagy Inhibition in <i>RAS</i> Mutant Cancer
title_full Clinical Translation of Combined MAPK and Autophagy Inhibition in <i>RAS</i> Mutant Cancer
title_fullStr Clinical Translation of Combined MAPK and Autophagy Inhibition in <i>RAS</i> Mutant Cancer
title_full_unstemmed Clinical Translation of Combined MAPK and Autophagy Inhibition in <i>RAS</i> Mutant Cancer
title_sort clinical translation of combined mapk and autophagy inhibition in <i>ras</i> mutant cancer
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/24c45a2ea6b847d1986090179b718cf8
work_keys_str_mv AT jenniferjlee clinicaltranslationofcombinedmapkandautophagyinhibitioninirasimutantcancer
AT vaibhavjain clinicaltranslationofcombinedmapkandautophagyinhibitioninirasimutantcancer
AT ravikamaravadi clinicaltranslationofcombinedmapkandautophagyinhibitioninirasimutantcancer
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