Towards exertion of immunotherapeutics in the treatment of colorectal cancer; adverse sides, challenges, and future directions

Abstract

Immunotherapy has growingly been prosperous as a promising therapeutic option for several kinds of solid tumors, such as colorectal cancer (CRC), subsequent to initial successful outcomes in the treatment of melanoma. The use of immunotherapy, like nivolumab and pembrolizumab (which are monoclonal antibodies against programmed cell death 1) has shown prosperous outcomes in a group of CRC patients who represent mismatch-repair-deficient and microsatellite instability-high (dMMR-MSI-H). However, a successful outcome of treatment by immune checkpoint inhibitors (ICIs) has not been observed in all of the metastatic CRC patients with dMMR-MSI-H tumors. ICIs are able to block the co-inhibitory signaling transduced in T cells, resulting in increased cytotoxic activity of T cells and efficient killing of tumor cells. In spite of availability of diverse immunotherapeutics in treatment of advanced CRC, a poor survival rate of such approaches has been reported along with challenges in the clinical practice. It is necessary to identify novel biomarkers and molecular signatures to approximate the outcome of ICI therapy in the metastatic CRC patients with dMMR-MSI-H tumors. Here we tried to clarify the current line of evidence regarding immunotherapeutics in the treatment of CRC, and discuss the challenges and hurdles in the management of these patients.

Keywords: Colorectal cancer; Immune checkpoint inhibitor; Immunotherapy; Microsatellite instability-high; Mismatch-repair-deficient; Monoclonal antibody.