Related Experiment Video

Updated: Jan 9, 2026

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
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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RASH3D19 mediates RAS activation through a positive feedback loop in KRAS-mutant cancer

Warapen Treekitkarnmongkol1, Hiroshi Katayama2, Deivendran Sankaran1,3

  • 1Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Nature Cell Biology
|December 1, 2025
PubMed

Insights

Researchers identified RASH3D19 as a key mediator in cancer cell growth and resistance to KRAS inhibitors. Targeting RASH3D19 may overcome resistance and shrink tumors in KRAS-mutant cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Actively investigating therapeutic targets for mutant KRAS-driven cancers.
  • Identifying feedback mechanisms driving adaptive resistance to KRAS inhibitors.

Purpose of the Study:

  • To identify RASH3D19 as a mediator of RAS pathway activation.
  • To investigate the role of RASH3D19 in KRAS-mutant cancer resistance.

Main Methods:

  • Investigated the KRAS-microRNA signaling axis.
  • Examined RASH3D19's role in RAS pathway activation and feedback loops.
  • Assessed the effects of RASH3D19 genetic deletion in vitro and in vivo.

Main Results:

  • Identified RASH3D19 as a mediator in a positive feedback loop involving KRAS-microRNA signaling.
  • Demonstrated that RASH3D19 promotes RAS pathway activation via EGFR complex interactions.
  • Genetic deletion of RASH3D19 inhibited cancer cell growth and sensitized cells to KRAS inhibitors.

Conclusions:

  • RASH3D19 is a crucial mediator in RAS pathway reactivation and adaptive resistance.
  • Targeting RASH3D19 offers a potential strategy to overcome resistance to KRAS inhibitors.
  • RASH3D19 inhibition may lead to tumor debulking in KRAS-mutant cancers.

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