Yanning Sun,* Li Ma,* Xiaofei Zhang,* Zhaoxia Wang

Cancer Medical Center, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Zhaoxia Wang, Cancer Medical Center, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210011, People’s Republic of China, Email wangzhaoxia@njmu.edu.cn

Abstract: Lung cancer is a malignant tumor with the highest morbidity and mortality rate worldwide, with nearly 2.5 million new cases and more than 1.8 million deaths reported globally in 2022. Lung cancer is broadly categorized into two main types: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), with NSCLC accounting for about 85% of all cases. Early-stage lung cancers often present without obvious symptoms, resulting in most patients being diagnosed at an advanced stage where traditional chemotherapy has limited efficacy. Recent advances in molecular biology have elucidated the pivotal role of gene mutations in tumor development, paving the way for targeted therapies that have markedly benefited patients. Beyond the well-known epidermal growth factor receptor (EGFR) mutation, an increasing number of new molecular targets have been identified, including ROS1 rearrangement, BRAF mutation, NTRK fusion, RET fusion, MET mutation, KRAS G12C mutation, HER2 mutation, ALK rearrangement, and NRG1 fusion. Some of these targeted therapies have already been approved by the Food and Drug Administration (FDA), and many others are currently undergoing clinical trials. This review summarizes recent advances in NSCLC treatment with molecular targets, highlighting progress, challenges, and their impact on patient prognosis.

Keywords: non-small cell lung cancer, rare mutations, targeted therapy, immunotherapy