Current and future perspectives in clinical practice in KRAS-mutated non-small cell lung cancer: a literature review

Background and Objective: The implementation in routine clinical practice of PD-L1 expression analysis and new massive sequencing techniques (NGS) has resulted in the creation of a molecular classification that leads on the most appropriate treatment for non-small cell lung cancer (NSCLC) is decided. Nowadays, specific treatments approved first-line against different mutations such as those targeting the EGFR, ALK, ROS1, KRAS, BRAF, RET or MET genes are commercially available. In this literature review we analyze the importance of the KRAS oncogene as a clinical biomarker in patients with NSCLC, its implication as a predictor of response to immunotherapy and the difficulties in developing specific drugs that act against mutations in this oncogene. Methods: The narrative review was conducted and carried out using the quality standards of narrative or literature review current guidelines. The reviews, clinical trials and studies included were found through searching several databases: PubMed, Cochrane, Science Direct, EMBASE, and the clinical trial registry ( www.clinicaltrials.gov ). The studies reviewing the main clinical trials that resulted in the approval of targeted therapies in NSCLC KRAS mutated and then the immunotherapy treatment in this type of lung cancer. Key Content and Findings: KRAS oncogene is one of the most frequently altered oncogenes in human cancers. In NSCLC it is altered in 20–30% of cases. In recent years, the identification of a new allosteric binding site in KRAS G12C has allowed the development of irreversible covalent inhibitors that have demonstrated their efficacy in daily clinical practice. However, other frequent mutations such as KRAS G12D and KRAS G12V still lack approved drugs although promising results have already been obtained in in-vitro and in-vivo clinical trials. There also appears to be a greater efficacy of response to immunotherapy in KRAS -mutated NSCLC, although this is a field under study. Conclusions: The KRAS gene has fundamental implications in NSCLC, both at the molecular and clinical levels. The correct and thorough characterisation of the different alterations and mutations of the KRAS gene will open up new avenues in the treatment of KRAS -mutated NSCLC, as well as personalising immunotherapy treatments in patients with these alterations.