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Updated: Oct 27, 2025
07:49
Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
Published on: July 17, 2019
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Autophagy Inhibition in BRAF-Driven Cancers
Mona Foth1, Martin McMahon1,2
1Huntsman Cancer Institute, Salt Lake City, UT 84112, USA.
Cancers
|July 24, 2021
Summary
BRAF-targeted cancer therapies show limited durability due to drug resistance. Autophagy, a cellular recycling process, increases with BRAF inhibition and may drive resistance, suggesting combined therapy as a future strategy.
Area of Science:
- Oncology
- Molecular Biology
- Cellular Biology
Background:
- BRAF-driven cancers like melanoma, lung, and thyroid cancer are treated with BRAF/MEK inhibitor combinations.
- Drug resistance limits the durability of patient responses to these therapies.
- Autophagy, a cellular recycling process, is upregulated in BRAF-inhibitor resistant cancers.
Purpose of the Study:
- To review the relationship between BRAF-targeted therapy and autophagy.
- To discuss potential therapeutic strategies combining oncogenic signaling inhibition with autophagy inhibition for BRAF-driven cancers.
Main Methods:
- Literature review of studies on BRAF-targeted therapy, drug resistance, and autophagy.
- Analysis of proposed mechanisms for BRAF inhibitor-induced autophagy.
Main Results:
- BRAF inhibitor resistance is associated with increased autophagy.
- Mechanisms include ER stress (GRP78), AMPK activation, and TFEB/TFE3 regulation via ERK1/2 or mTOR.
- Autophagy may promote tumor progression and protect cancer cells from therapy.
Conclusions:
- Autophagy plays a significant role in BRAF inhibitor resistance.
- Combined inhibition of oncogenic signaling and autophagy presents a promising future treatment strategy for BRAF-driven cancers.
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