Anti-PD-1 combined with targeted therapy: Theory and practice in gastric and colorectal cancer

Abstract

Gastric cancer (GC) and colorectal cancer (CRC) are frequent and aggressive malignancies worldwide. Despite the emergence of various therapeutic regimens, the prognosis of gastric and colorectal cancer is relatively poor. Immunotherapy targeting PD-1 is one of the most prevalent approaches, but it has a low response rate in most patients, particularly those with microsatellite stability (MSS). Recently, some targeted drugs have been found to remarkably enhance the anti-tumor immunity of cancer models, mainly through increasing the level of CD8⁺ T cells, M1-type macrophages, expression of PD-L1, and decreasing the level of regulatory T cells and M2 macrophages. The above finding implies that the combination of anti-PD-1 and targeted therapies may be a potential treatment for gastric and colorectal cancer patients. Although many encouraging preclinical results have been shown, the clinical outcomes were not approving enough. To further enhance the therapeutic efficacy and improve the prognosis in GC and CRC patients, deeper and larger-scale studies should be done to determine the complicated interactions between the two therapies and the concrete use of combination regimens.

Keywords: Anti-PD-1; Colorectal Cancer; Combination; Gastric Cancer; Immunotherapy; Targeted therapy.