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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| Main Authors: | , , |
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| Format: | article |
| Language: | EN |
| Published: |
MDPI AG
2021
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| Subjects: | |
| Online Access: | https://doaj.org/article/24c45a2ea6b847d1986090179b718cf8 |
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| Summary: | <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. |
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