A Narrative Review of the Role of Immunotherapy in Metastatic Carcinoma of the Colon Harboring a BRAF Mutation

Abstract

Patients affected by metastatic carcinoma of the colon/rectum (mCRC) harboring mutations in the BRAF gene (MBRAF) respond poorly to conventional therapy and have a prognosis worse than that of patients without mutations. Despite the promising outcomes of targeted therapy utilizing multi-targeted inhibition of the mitogen-activated protein kinase (MAPK) signaling system, the therapeutic efficacy, especially for the microsatellite stable/DNA proficient mismatch repair (MSS/PMMR) subtype, remains inadequate. Patients with MBRAF/mCRC and high microsatellite instability or DNA deficient mismatch repair (MSI-H/DMMR) exhibit a substantial tumor mutation burden, suggesting a high probability of response to immunotherapy. It is widely acknowledged that MSS/pMMR/mCRC is an immunologically "cold" malignancy that exhibits resistance to immunotherapy. The integration of targeted therapy and immunotherapy may enhance clinical outcomes in patients with MBRAF/mCRC. Efforts to enhance outcomes are exclusively focused on MSS/DMMR-BRAF mutant cancers, which constitute the largest proportion. This review evaluates the clinical efficacy and advancement of novel immune checkpoint blockade therapies for MSI-H/DMMR and MSS/PMMR BRAF mutant mCRC. We examine potential indicators in the tumor immune milieu for forecasting immunotherapeutic response in BRAF mutant mCRC.