The Path to Personalized Treatment in KRAS-Mutant Non-Small Cell Lung Cancer: A Review of Targeted Therapies and Immunotherapy.

Abstract

To summarize the targeted therapies and immunotherapy of Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutant non-small cell lung cancer (NSCLC), and discuss the ongoing clinical trials. KRAS mutations occur in about 30% of patients with NSCLC and are the second most frequent genetic variation in lung cancer. It has been considered "undruggable" for 40 years until the discovery of a direct inhibitor of KRAS G12C. The promising direct KRAS G12C inhibitors such as sotorasib and MRTX849 have made a breakthrough with promising anti-tumor effects in patients with KRAS G12C-mutant advanced/metastatic NSCLC post one prior line of therapy. Following the success of immune checkpoint inhibitors (ICIs) in NSCLC, many patients harboring KRAS mutations can benefit from ICIs. However, due to disease heterogeneity, the prognosis of patients remains unsatisfactory, leaving room for personalized treatment options, such as new targeted therapies and other therapies. In this review, we aim to dissect the strategies of clinical trials in these tumors, shifting from a few chemotherapy options to targeted and immunotherapy, in the context of molecular selection of KRAS-mutant NSCLC subtypes.