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Updated: Mar 19, 2026

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The Hippo effector YAP regulates the response of cancer cells to MAPK pathway inhibitors

Luping Lin1, Trever G Bivona1

  • 1Division of Hematology and Medical Oncology; University of California San Francisco; San Francisco, CA USA; Helen Diller Family Comprehensive Cancer Center; University of California San Francisco; San Francisco, CA USA.

Molecular & Cellular Oncology
|June 17, 2016
PubMed

Insights

Resistance to RAF-MEK inhibitors in cancers like melanoma is a challenge. Yes-associated protein 1 (YAP1) drives this resistance, suggesting co-targeting YAP1 with RAF-MEK inhibitors could improve treatment outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • RAF- and MEK-targeted therapies show promise for BRAF(V600E) melanoma and other cancers.
  • Therapeutic resistance to these targeted agents is a significant clinical hurdle.

Purpose of the Study:

  • To identify novel mechanisms of resistance to RAF-MEK inhibition.
  • To investigate the role of yes-associated protein 1 (YAP1) in mediating resistance to RAF-MEK targeted therapies.

Main Methods:

  • Utilized genetic and pharmacological approaches in BRAF- and RAS-mutant cancer models.
  • Assessed the impact of YAP1 modulation on cellular response to RAF-MEK inhibitors.

Main Results:

  • Identified yes-associated protein 1 (YAP1) as a key mediator of resistance to RAF-MEK inhibitors.
  • Demonstrated that YAP1 activation confers resistance in both BRAF- and RAS-mutant cancers.

Conclusions:

  • YAP1 represents a critical resistance mechanism against RAF-MEK targeted therapies.
  • Co-targeting YAP1 alongside RAF-MEK inhibitors presents a promising strategy to overcome resistance and improve patient outcomes in relevant cancers.
Keywords:
BRAFHippoMEKRASYAPresistancetargeted therapy

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