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A Comprehensive Review on MAPK: A Promising Therapeutic Target in Cancer

Cornelia Braicu1, Mihail Buse2, Constantin Busuioc3

  • 1Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 23 Marinescu Street, 40015 Cluj-Napoca, Romania. braicucornelia@yahoo.com.

Cancers
|October 27, 2019
PubMed

Insights

The mitogen-activated protein kinase (MAPK) pathway regulates cellular responses but can be altered in cancer. Inhibiting MAPK often leads to resistance via compensatory pathways, necessitating novel combinatorial therapies.

Area of Science:

  • Cellular Biology
  • Molecular Oncology
  • Signal Transduction

Background:

  • The mitogen-activated protein kinase (MAPK) pathway is crucial for translating extracellular signals into intracellular responses.
  • Dysregulation of MAPK signaling cascades is implicated in various diseases, notably cancer, due to genetic and epigenetic alterations.
  • While extensively studied, the precise regulation and action models of MAPK signaling in both health and disease require further elucidation.

Purpose of the Study:

  • To discuss new insights into the complex cell signaling pathway of MAPK.
  • To explore MAPK's roles in maintaining normal cellular function and its implications in cancer therapy.
  • To examine the activation of compensatory pathways in response to MAPK inhibition and its impact on cancer treatment.

Main Methods:

  • Literature review and synthesis of current research on MAPK signaling.
  • Analysis of preclinical and clinical studies investigating MAPK pathway alterations in cancer.
  • Discussion of resistance mechanisms to MAPK inhibitors and potential therapeutic strategies.

Main Results:

  • MAPK pathway alterations are linked to cancer development and progression.
  • MAPK inhibitors frequently encounter resistance mediated by compensatory feedback loops involving tumor cells and the microenvironment.
  • Understanding these compensatory mechanisms is vital for overcoming therapeutic resistance.

Conclusions:

  • MAPK signaling is a complex pathway with significant roles in cellular homeostasis and cancer.
  • Therapeutic resistance to MAPK inhibitors is a major challenge in cancer management.
  • Novel combinatorial therapies targeting compensatory pathways are essential for effective cancer treatment and improved patient outcomes.
Keywords:
MAPKcancerdrug resistancemolecular mechanisms

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