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Targeting MSS colorectal cancer with immunotherapy: are we turning the corner?

Chongkai Wang1, Marwan Fakih1

  • 1Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.

Expert Opinion on Biological Therapy
|May 25, 2021
PubMed
Abstract

Insights

Microsatellite stable colorectal cancer is resistant to immunotherapy. Combination strategies and predictive biomarkers are being explored to improve patient response to checkpoint inhibition therapies.

Area of Science:

  • Oncology
  • Immunology
  • Cancer Research

Background:

  • Immunotherapy, specifically checkpoint inhibition, demonstrates significant antitumor effects in microsatellite instability-high (MSI-H) metastatic cancers.
  • Microsatellite stable (MSS) colorectal cancer has historically shown resistance to immunotherapy.

Purpose of the Study:

  • To review current strategies aimed at overcoming immunotherapy resistance in MSS colorectal cancer.
  • To highlight emerging combination therapies and the importance of predictive biomarkers.

Main Methods:

  • Review of current scientific literature and clinical trial data on immunotherapy for MSS colorectal cancer.
  • Analysis of emerging combination strategies including immune modulators, Stat3 inhibitors, and bispecific T-cell engagers.
  • Evaluation of potential predictive biomarkers for treatment response.

Main Results:

  • Combination therapies, such as regorafenib with checkpoint blockade, show promise in enhancing responsiveness in MSS colorectal cancer.
  • Other combination strategies, including Stat3 inhibitors and bispecific T-cell engagers, are also showing clinical activity.
  • Liver metastases are identified as a potential biomarker predicting lack of benefit from PD-1 targeting, even with combination therapies.

Conclusions:

  • Overcoming immunotherapy resistance in MSS colorectal cancer requires novel therapeutic strategies and a deeper understanding of resistance mechanisms.
  • Identifying predictive biomarkers is crucial for the successful clinical implementation of immunotherapy in MSS colorectal cancer.
  • Further research is needed to develop and validate new approaches to improve treatment outcomes.
Keywords:
MSSPD-1PD-l1colorectal cancerimmunotherapymetastatic

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