Strategy to targeting the immune resistance and novel therapy in colorectal cancer

Cancer Med. 2018 May;7(5):1578-1603. doi: 10.1002/cam4.1386. Epub 2018 Apr 15.

Abstract

Assessing the CRC subtypes that can predict the outcome of colorectal cancer (CRC) in patients with immunogenicity seems to be a promising strategy to develop new drugs that target the antitumoral immune response. In particular, the disinhibition of the antitumoral T-cell response by immune checkpoint blockade has shown remarkable therapeutic promise for patients with mismatch repair (MMR) deficient CRC. In this review, the authors provide the update of the molecular features and immunogenicity of CRC, discuss the role of possible predictive biomarkers, illustrate the modern immunotherapeutic approaches, and introduce the most relevant ongoing preclinical study and clinical trials such as the use of the combination therapy with immunotherapy. Furthermore, this work is further to understand the complex interactions between the immune surveillance and develop resistance in tumor cells. As expected, if the promise of these developments is fulfilled, it could develop the effective therapeutic strategies and novel combinations to overcome immune resistance and enhance effector responses, which guide clinicians toward a more "personalized" treatment for advanced CRC patients.

Keywords: Colorectal cancer; gene phenotype; immune resistance; immunotherapy; subtypes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biomarkers, Tumor / immunology*
  • Clinical Trials as Topic
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / immunology
  • DNA Mismatch Repair
  • Drug Resistance, Neoplasm
  • Humans
  • Immunotherapy / methods*
  • Precision Medicine
  • Treatment Outcome
  • Tumor Microenvironment

Substances

  • Biomarkers, Tumor