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Targeting MAPK Signaling in Cancer: Mechanisms of Drug Resistance and Sensitivity

Shannon Lee1, Jens Rauch1,2, Walter Kolch1,3

  • 1Systems Biology Ireland, School of Medicine, University College Dublin, Dublin 4, Ireland.

International Journal of Molecular Sciences
|February 13, 2020
PubMed

Insights

Mitogen-activated protein kinase (MAPK) pathways significantly influence cancer drug response. Understanding how stress-activated MAPKs, metabolic, and epigenetic changes affect drug sensitivity offers new therapeutic strategies.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Cancer Research

Background:

  • Mitogen-activated protein kinase (MAPK) pathways are crucial for cellular functions and are often dysregulated in diseases like cancer.
  • These pathways play a significant role in regulating cell growth, differentiation, and survival.
  • Aberrations in MAPK signaling are implicated in the development and progression of various cancers.

Purpose of the Study:

  • To investigate the role of MAPK pathways in modulating drug sensitivity and resistance in cancer.
  • To explore the mechanisms by which stress-activated MAPK pathways (p38 MAPK, JNK) affect cancer cell responses to chemotherapy and targeted therapies.
  • To discuss the influence of metabolic and epigenetic alterations on MAPK-mediated drug resistance and identify potential therapeutic opportunities.

Main Methods:

  • Review of current literature on MAPK pathways in cancer drug response.
  • Focus on stress-activated pathways like p38 MAPK and Jun N-terminal kinases (JNK).
  • Discussion of extracellular signal-regulated kinase (ERK) pathway findings and integration of metabolic and epigenetic factors.

Main Results:

  • MAPK pathways, particularly stress-activated ones, are key regulators of cancer cell sensitivity and resistance to various drugs.
  • Metabolic and epigenetic aberrations interact with MAPK signaling to influence therapeutic outcomes.
  • Specific MAPK pathways like p38 and JNK significantly impact responses to chemotherapy and targeted agents.

Conclusions:

  • Targeting MAPK pathways, especially stress-activated ones, holds promise for overcoming drug resistance in cancer.
  • Understanding the interplay between MAPK signaling, metabolism, and epigenetics can reveal novel therapeutic strategies.
  • Further research into these complex interactions may lead to improved cancer treatment outcomes.
Keywords:
ERKJNKMAPKcancercombination therapydrug resistanceepigeneticsmetabolismp38

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