Related Experiment Video

Updated: Feb 13, 2026

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors
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A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors

Published on: December 7, 2014

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BRAF and MEK Inhibitors: Use and Resistance in BRAF-Mutated Cancers

Jaquelyn N Sanchez1, Ton Wang2, Mark S Cohen3,4

  • 1Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI, USA.

Drugs
|March 1, 2018
PubMed

Insights

Targeting the MAPK/ERK pathway with small-molecule inhibitors is crucial for treating cancers. However, understanding drug resistance mechanisms is vital for overcoming patient relapse and improving therapeutic outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • The mitogen activated protein kinase/extracellular signal-related kinase (MAPK/ERK) pathway is essential for normal mammalian cell functions.
  • Dysregulation of the MAPK/ERK pathway is implicated in various hematologic and solid tumors.
  • Constitutive activation, often due to mutations in rapidly accelerating fibrosarcoma (RAF) kinase, drives cancer progression.

Purpose of the Study:

  • To review the approval and clinical application of MAPK/ERK pathway inhibitors in cancer treatment.
  • To elucidate the primary mechanisms of acquired drug resistance to these targeted therapies.
  • To highlight the need for further research into resistance pathways.

Main Methods:

  • Literature review of approved MAPK/ERK pathway inhibitors.
  • Analysis of clinical trial data and patient outcomes.
  • Synthesis of current knowledge on resistance mechanisms.

Main Results:

  • Several small-molecule inhibitors targeting the MAPK/ERK pathway are approved for cancer therapy.
  • These inhibitors are used as monotherapy or in combination regimens.
  • Drug resistance leading to patient relapse is a significant clinical challenge.

Conclusions:

  • MAPK/ERK pathway inhibitors represent a significant advancement in cancer treatment.
  • Understanding and overcoming resistance mechanisms is critical for sustained therapeutic efficacy.
  • Further investigation into resistance pathways is warranted to improve patient outcomes.

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