The p38 MAPK Signaling Activation in Colorectal Cancer upon Therapeutic Treatments

Int J Mol Sci. 2020 Apr 16;21(8):2773. doi: 10.3390/ijms21082773.

Abstract

Pharmacological treatment of colorectal carcinoma currently proceeds through the administration of a combination of different chemotherapeutic agents. In the case of rectal carcinoma, radiation therapy also represents a therapeutic strategy. In an attempt at translating much-needed new targeted therapy to the clinics, p38 mitogen activated protein kinase (MAPK) inhibitors have been tested in clinical trials involving colorectal carcinoma patients, especially in combination with chemotherapy; however, despite the high expectations raised by a clear involvement of the p38 MAPK pathway in the response to therapeutic treatments, poor results have been obtained so far. In this work, we review recent insights into the exact role of the p38 MAPK pathway in response to currently available therapies for colorectal carcinoma, depicting an intricate scenario in which the p38 MAPK node presents many opportunities, as well as many challenges, for its perspective exploitation for clinical purposes.

Keywords: 5-fluorouracil; colorectal cancer; irinotecan; oxaliplatin; p38 MAPK; radiotherapy; target therapy; therapeutic treatments.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / drug effects
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / radiotherapy
  • Fluorouracil / pharmacology
  • Fluorouracil / therapeutic use
  • Humans
  • Oxaliplatin / pharmacology
  • Oxaliplatin / therapeutic use
  • Protein Isoforms / metabolism
  • Signal Transduction / drug effects
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Antineoplastic Agents
  • Protein Isoforms
  • Oxaliplatin
  • p38 Mitogen-Activated Protein Kinases
  • Fluorouracil