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Approaching the challenges of MKK3/p38delta MAPK targeting for therapeutic purpose in colorectal cancer

Lorenzo Stramucci1, Gianluca Bossi2

  • 1Oncogenomic and Epigenetic Unit, Department of Diagnostic Research and Technological Innovation, IRCCS - Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy.

Journal of Experimental & Clinical Cancer Research : CR
|December 29, 2019
PubMed

Insights

Mitogen-activated protein kinase kinase 3 (MKK3) activates p38delta MAPK, impacting colorectal cancer (CRC) treatment efficacy. This axis may hinder 5-fluorouracil (5-FU) effectiveness in CRC.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Signal Transduction

Background:

  • MKK3, a dual specificity kinase, is an upstream activator of p38 MAPK proteins.
  • MKK3 was identified as a gain-of-function target gene upregulated by mutant p53 (mutp53) in various tumor models.
  • Investigated MKK3 functions in cancer using colorectal cancer (CRC) cell lines and primary colonocytes.

Discussion:

  • MKK3 specifically activates the p38delta MAPK protein.
  • p38delta MAPK signaling is further enhanced by 5-fluorouracil (5-FU) chemotherapy.
  • The MKK3/p38delta MAPK axis is implicated in reducing 5-FU treatment efficacy in CRC.

Key Insights:

  • MKK3 activates p38delta MAPK in colorectal cancer.
  • This activation is modulated by 5-FU chemotherapy.
  • The MKK3/p38delta MAPK pathway contributes to 5-FU resistance in CRC.

Outlook:

  • Further research into the MKK3/p38delta MAPK axis could reveal new therapeutic strategies for CRC.
  • Understanding this pathway's role in chemoresistance is crucial for improving patient outcomes.
  • Contextualizing these findings within the broader p38 MAPK field in cancer is essential.
Keywords:
ChemotherapyColorectal CancerCombined treatmentsMKK3 / p38 MAPK signallingTarget therapyp38 delta MAPK

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