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

Int J Mol Sci. 2020 Feb 7;21(3):1102. doi: 10.3390/ijms21031102.

Abstract

Mitogen-activated protein kinase (MAPK) pathways represent ubiquitous signal transduction pathways that regulate all aspects of life and are frequently altered in disease. Here, we focus on the role of MAPK pathways in modulating drug sensitivity and resistance in cancer. We briefly discuss new findings in the extracellular signaling-regulated kinase (ERK) pathway, but mainly focus on the mechanisms how stress activated MAPK pathways, such as p38 MAPK and the Jun N-terminal kinases (JNK), impact the response of cancer cells to chemotherapies and targeted therapies. In this context, we also discuss the role of metabolic and epigenetic aberrations and new therapeutic opportunities arising from these changes.

Keywords: ERK; JNK; MAPK; cancer; combination therapy; drug resistance; epigenetics; metabolism; p38.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Resistance, Neoplasm*
  • Epigenesis, Genetic
  • Humans
  • MAP Kinase Signaling System*
  • Molecular Targeted Therapy / methods*
  • Neoplasms / drug therapy
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • p38 Mitogen-Activated Protein Kinases