Overview of Current Immunotherapies Targeting Mutated KRAS Cancers

Abstract

The occurrence of somatic substitution mutations of the KRAS proto-oncogene is highly prevalent in certain cancer types, which often leads to constant activation of proliferative pathways and subsequent neoplastic transformation. It is often seen as a gateway mutation in carcinogenesis and has been commonly deemed as a predictive biomarker for poor prognosis and relapse when conventional chemotherapeutics are employed. Additionally, its mutational status also renders EGFR targeted therapies ineffective owing to its downstream location. Efforts to discover new approaches targeting this menacing culprit have been ongoing for years without much success, and with incidences of KRAS positive cancer patients being on the rise, researchers are now turning towards immunotherapies as the way forward. In this scoping review, recent immunotherapeutic developments and advances in both preclinical and clinical studies targeting K-ras directly or indirectly via its downstream signal transduction machinery will be discussed. Additionally, some of the challenges and limitations of various K-ras targeting immunotherapeutic approaches such as vaccines, adoptive T cell therapies, and checkpoint inhibitors against KRAS positive cancers will be deliberated.

Keywords: Cancer; Cancer vaccines; Immunotherapies; KRAS mutation; RTK; Targeted therapies..