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Updated: Sep 8, 2025

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Targeting pathological ERK1/2 signaling in cancer and beyond

Constanze Schanbacher1, Maria-Elisabeth Goebeler2, Brenda Gerull3

  • 1Institute of Pharmacology and Toxicology, University of Würzburg, 97078 Würzburg, Germany.

Trends in Molecular Medicine
|September 6, 2025
PubMed

Insights

Targeting the RAF-MEK-ERK1/2 pathway offers new therapeutic strategies for diseases beyond cancer. Lessons from cancer drug development inform treatments for conditions like RASopathies involving ERK1/2 dysregulation.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • The RAF-MEK-ERK1/2 pathway is crucial in cellular signaling and its dysregulation contributes to various diseases, notably cancer.
  • Targeted therapies against this pathway have been developed for cancer, leading to increased understanding of ERK1/2 functions.

Purpose of the Study:

  • To review the latest advancements in targeting MEK1/2 and ERK1/2 kinases.
  • To explore the application of cancer therapy insights to other diseases with ERK1/2 pathway involvement.

Main Methods:

  • Literature review focusing on MEK and ERK targeting strategies.
  • Analysis of drug development, clinical outcomes, and resistance mechanisms in cancer therapy.
  • Exploration of ERK1/2 dysregulation in non-cancerous conditions.

Main Results:

  • Targeting MEK1/2 and ERK1/2 has shown promise in cancer treatment, yielding valuable data on pathway modulation.
  • Understanding of ERK1/2's physiological and pathological roles has expanded significantly through cancer research.
  • Potential for repurposing these therapeutic strategies for genetic disorders like RASopathies is emerging.

Conclusions:

  • Targeting the RAF-MEK-ERK1/2 pathway is a dynamic field with implications extending beyond oncology.
  • Insights gained from cancer therapies provide a foundation for novel treatment approaches in other ERK1/2-related disorders.
  • Further research into MEK and ERK targeting may unlock new therapeutic avenues for a broader range of diseases.
Keywords:
ERK1/2MAPKRASopathiescancercardiotoxicityinhibitors

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