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

Lorenzo Stramucci, Gianluca Bossi

Research output: Contribution to journalReview articlepeer-review

Abstract

MKK3 is a member of the dual specificity kinase group specific upstream activator of p38 MAPK proteins. We originally identified MKK3 as mutant p53 (mutp53) gain-of-function (GOF) upregulated target gene in different tumor models. To deeply investigate the MKK3 functions in cancer, taking advantage of a panel of authenticated colorectal cancer (CRC) lines and primary colonocytes, we found that MKK3 activates specifically p38delta MAPK protein, which signaling is further triggered by 5-fluorouracil (5-FU) treatments, a largely adopted chemotherapeutic drug in CRC clinical practice. The overall achieved results proposed the MKK3/p38delta MAPK as relevant molecular axis involved in abrogating efficacy to 5-FU treatments in CRC. This commentary will provide an overall discussion of the results that have been achieved contextualizing them in the overview of the knowledge in the p38 MAPK field in cancer disease.

Original languageEnglish
JournalJournal of Experimental and Clinical Cancer Research
Volume38
Issue number1
DOIs
Publication statusPublished - Dec 27 2019

Keywords

  • Chemotherapy
  • Colorectal Cancer
  • Combined treatments
  • MKK3 / p38 MAPK signalling
  • p38 delta MAPK
  • Target therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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