2023/07/11 by Gozde Kavgaci, Suayib Yalcin, Sahin, Ibrahim Halil +2
#combination therapy #immune checkpoint inhibitors #microsatellite stable colorectal cancer #molecular subtypes #tumor microenvironment
paper · doi:10.17605/osf.io/gz7rx
The use of immune checkpoint inhibitors (ICIs) has revolutionized cancer care, particularly in immune-inflamed tumors with high mutational burdens. However, their effectiveness in microsatellite stable (MSS) colorectal cancer (CRC) is limited. This systematic review aims to evaluate the efficacy of ICIs in MSS CRC and explore promising combination strategies. A comprehensive search identified 52 clinical trials included in the review. Monotherapy with ICIs demonstrated limited clinical activity in MSS CRC, with response rates below 10%. Combination strategies involving tyrosine kinase inhibitors (TKIs), chemotherapy, and other tumor microenvironment modifications were investigated. Combination therapy with anti-VEGF agents yielded varying results, with some studies reporting improved outcomes. The combination of ICIs with chemotherapy showed promise, especially in early treatment settings. Additionally, combinations involving BRAF inhibitors, CAR-T therapy, and TGF beta inhibitors were studied, but further research is needed to optimize these approaches. Ongoing studies are evaluating various combination regimens, including ICI-TKI and ICI-chemotherapy. Patient stratification based on molecular subtypes, such as consensus molecular subtypes (CMS), may facilitate individualized treatment and improve outcomes. In conclusion, while ICI monotherapy has limited efficacy in MSS CRC, combination strategies hold promise for enhancing patient outcomes. Further research is necessary to identify optimal combination approaches and predictive biomarkers for treatment response.