Related Experiment Video

Updated: Sep 22, 2025

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

6.2K

Drug resistance in targeted cancer therapies with RAF inhibitors

Ufuk Degirmenci1,2, Jiajun Yap1,3,2, Yuen Rong M Sim1

  • 1The Laboratory of Cancer Signaling, National Cancer Centre Singapore, Singapore 169610, Singapore.

Cancer Drug Resistance (Alhambra, Calif.)
|May 18, 2022
PubMed

Insights

Targeting the RAS/RAF/MEK/ERK pathway shows promise in cancer treatment. However, drug resistance limits efficacy, driving the development of next-generation RAF inhibitors for improved cancer therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Hyperactive RAS/RAF/MEK/ERK signaling is crucial in cancer development.
  • RAF inhibitors are approved for specific mutations like BRAF(V600E).
  • Drug resistance and intrinsic resistance in RAS-mutated cancers limit current therapies.

Purpose of the Study:

  • To summarize findings on RAF inhibitor resistance mechanisms.
  • To discuss challenges in developing next-generation RAF inhibitors.
  • To provide insights for improving targeted cancer therapy.

Main Methods:

  • Review of recent mechanistic studies on RAF inhibitor resistance.
  • Analysis of genetic alterations activating the RAS/RAF/MEK/ERK pathway.
  • Evaluation of clinical data for first- and second-generation RAF inhibitors.

Main Results:

  • First-generation RAF inhibitors show efficacy but face rapid resistance.
  • Cancers with hyperactive RAS often exhibit intrinsic resistance to RAF inhibitors.
  • Second-generation RAF inhibitors are under development to overcome resistance.

Conclusions:

  • Understanding resistance mechanisms is key to improving RAF inhibitor therapy.
  • Next-generation RAF inhibitors aim for a better therapeutic index.
  • Further research can enhance targeted cancer treatment strategies.
Keywords:
RAF inhibitorsRAF/KSR family kinaseRAS/RAF/MEK/ERK signalingdrug resistanceoncogenic mutationregulatory spinetargeted therapy

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