Advancing translational research for colorectal immuno-oncology

Colorectal cancer (CRC) is a common and deadly disease. Unfortunately, immune checkpoint inhibitors (ICIs) fail to elicit effective anti-tumour responses in the vast majority of CRC patients. Patients that are most likely to respond are those with DNA mismatch repair deficient (dMMR) and microsatell...

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Bibliographic Details
Published in:British journal of cancer 2023-10, Vol.129 (9), p.1442-1450
Main Authors: Thomas, Elaine M., Wright, Josephine A., Blake, Stephen J., Page, Amanda J., Worthley, Daniel L., Woods, Susan L.
Format: Article
Language:English
Subjects:
631/67/1504/1885/1393
631/67/1504/1885/1777
631/67/70
Animal models
Animals
Biomedical and Life Sciences
Biomedicine
Brain Neoplasms
Cancer immunotherapy
Cancer Research
Colorectal cancer
Colorectal carcinoma
Colorectal Neoplasms
DNA Mismatch Repair
DNA repair
Drug Resistance
Epidemiology
Humans
Immune checkpoint inhibitors
Immunotherapy
Medical Oncology
Medical research
Mice
Microsatellite Instability
Mismatch repair
Molecular Medicine
Oncology
Review
Review Article
Translational Research, Biomedical
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Summary:Colorectal cancer (CRC) is a common and deadly disease. Unfortunately, immune checkpoint inhibitors (ICIs) fail to elicit effective anti-tumour responses in the vast majority of CRC patients. Patients that are most likely to respond are those with DNA mismatch repair deficient (dMMR) and microsatellite instability (MSI) disease. However, reliable predictors of ICI response are lacking, even within the dMMR/MSI subtype. This, together with identification of novel mechanisms to increase response rates and prevent resistance, are ongoing and vitally important unmet needs. To address the current challenges with translation of early research findings into effective therapeutic strategies, this review summarises the present state of preclinical testing used to inform the development of immuno-regulatory treatment strategies for CRC. The shortfalls and advantages of commonly utilised mouse models of CRC, including chemically induced, transplant and transgenic approaches are highlighted. Appropriate use of existing models, incorporation of patient-derived data and development of cutting-edge models that recapitulate important features of human disease will be key to accelerating clinically relevant research in this area.
ISSN:0007-0920
1532-1827
DOI:10.1038/s41416-023-02392-x