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Strategy to targeting the immune resistance and novel therapy in colorectal cancer
Wang Gang1, Jun-Jie Wang1, Rui Guan2
1Department of Pharmaceutics, Shanghai Eighth People's Hospital, Jiangsu University, 200235, Shanghai, China.
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.
Insights
Identifying colorectal cancer (CRC) subtypes that predict patient outcomes and immunogenicity is key for developing targeted therapies. Immune checkpoint blockade shows promise, especially for mismatch repair deficient CRC, offering new treatment avenues.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- Colorectal cancer (CRC) subtypes with predictive immunogenicity are crucial for targeted drug development.
- Immune checkpoint blockade demonstrates significant therapeutic potential in mismatch repair deficient CRC by disinhibiting anti-tumor T-cell responses.
Purpose of the Study:
- To review the molecular features and immunogenicity of CRC.
- To discuss predictive biomarkers and modern immunotherapeutic approaches for CRC.
- To highlight ongoing preclinical and clinical trials, including combination therapies.
Main Methods:
- Literature review of molecular features, immunogenicity, biomarkers, and immunotherapies in CRC.
- Analysis of ongoing preclinical studies and clinical trials.
- Exploration of immune surveillance and tumor resistance mechanisms.
Main Results:
- Update on molecular characteristics and immunogenicity of CRC.
- Discussion on the role of predictive biomarkers in immunotherapy response.
- Overview of current and future immunotherapeutic strategies, including combination treatments.
Conclusions:
- Understanding CRC immunogenicity and molecular subtypes can guide personalized treatment strategies.
- Combination therapies hold promise for overcoming immune resistance and enhancing effector responses in advanced CRC.
- Further research into immune interactions is essential for developing effective therapeutic strategies.
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