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Emerging Insight into MAPK Inhibitors and Immunotherapy in Colorectal Cancer

Massimo Pancione1, Guido Giordano2, Pietro Parcesepe3

  • 1Department of Sciences and Technologies, University of Sannio, Via Port'Arsa, 1182100 Benevento. Italy.

Current Medicinal Chemistry
|March 2, 2017
PubMed

Insights

Targeted therapies for colorectal cancer (CRC) impact immune responses. Understanding MAPK signaling in the tumor microenvironment can guide new drug development for improved CRC treatment.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Colorectal cancer (CRC) progression and therapy resistance involve complex genetic and non-genetic molecular alterations.
  • Targeted therapies can influence tumor biology and host immune responses, necessitating a deeper understanding of tumor microenvironments.
  • Mitogen-activated protein kinase (MAPK) superfamily alterations, particularly ERKs and p38 MAPKs, are implicated in inflammation, anti-tumor immunity, and metastatic potential.

Purpose of the Study:

  • To comprehensively define mechanisms by which immune cells regulate T-cell activity within tumor microenvironments.
  • To explore the role of MAPK signaling in colorectal cancer progression, therapy resistance, and immune evasion.
  • To translate current knowledge into novel drug development strategies combining targeted therapies and immunotherapies for CRC.

Main Methods:

  • Review and synthesis of existing literature on molecular alterations in CRC.
  • Analysis of MAPK superfamily signaling pathways (ERKs, p38 MAPKs) in tumor biology and immune response.
  • Exploration of mechanisms linking oncogenic signals, cellular homeostasis, and clonal evolution during targeted therapies.

Main Results:

  • Alterations in MAPK signaling pathways significantly influence inflammatory responses and anti-tumor immunity.
  • MAPK activation, especially ERKs, is frequently observed at relapse and contributes to clonal evolution under targeted therapy.
  • Understanding these pathways offers insights into modulating tumor antigenicity and enhancing anti-tumor immune responses.

Conclusions:

  • Targeted therapies and immunotherapies can be combined for improved colorectal cancer treatment outcomes.
  • Further research into MAPK signaling and immune cell interactions within the tumor microenvironment is crucial for developing effective CRC therapies.
  • Translating knowledge of molecular alterations into drug development strategies holds promise for increasing tumor antigenicity and boosting anti-tumor immunity.
Keywords:
ERKsMAPKscolorectal cancerimmune check point inhibitorsimmune resistanceimmunotherapyp38 MAPKs

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