TY - JOUR
T1 - Advancing translational research for colorectal immuno-oncology
AU - Thomas, Elaine M.
AU - Wright, Josephine A.
AU - Blake, Stephen J.
AU - Page, Amanda J.
AU - Worthley, Daniel L.
AU - Woods, Susan L.
N1 - Funding Information:
This study was supported by grants from the National Health and Medical Research Council (APP1184925 to SLW), National Cancer Institute (1R01CA241728-01A1 to DLW). EMT is supported by a University of Adelaide Research Scholarship. All figures and tables were created with BioRender.com.
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/8/10
Y1 - 2023/8/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85167516578&partnerID=8YFLogxK
U2 - 10.1038/s41416-023-02392-x
DO - 10.1038/s41416-023-02392-x
M3 - Review article
AN - SCOPUS:85167516578
SN - 0007-0920
VL - 129
SP - 1442
EP - 1450
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 9
ER -