Min Tang,1,2 Yijun Wu,1,2 Xiufeng Bai,3,4 You Lu1,2 

1Division of Thoracic Tumor Multimodality Treatment and Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Laboratory of Clinical Cell Therapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Laboratory of Human Disease and Immunotherapies, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 4Institute of Inflammation and Immunology (I3), Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, People’s Republic of China

Correspondence: You Lu, West China Hospital, West China School of Clinical Medicine, Sichuan University, 37, Guoxue Lane, Chengdu, 610041, Email radyoulu@hotmail.com

Abstract: Rat sarcoma virus (RAS) GTPase is one of the most important drivers of non-small cell lung cancer (NSCLC). RAS has three different isoforms (Harvey rat sarcoma viral oncogene homolog [HRAS], Kirsten rat sarcoma viral oncogene homolog [KRAS] and Neuroblastoma ras viral oncogene homolog [NRAS]), of which KRAS is most commonly mutated in NSCLC. The mutated KRAS protein was historically thought to be “undruggable” until the development of KRASG12C inhibitors. In this review, from the aspect of brain metastasis, we aim to provide an overview of the advances in therapies that target KRASG12C, the limitations of the current treatments, and future prospects in patients with KRAS p.G12C mutant NSCLC.

Keywords: KRAS, G12C, non-small cell lung cancer, brain metastases