Structure-Guided Strategies of Targeted Therapies for Patients with <i>EGFR</i>-Mutant Non–Small Cell Lung Cancer
Zhenfang Du,
Jinghan Sun,
Yunkai Zhang,
Nigaerayi Hesilaiti,
Qi Xia,
Heqing Cui,
Na Fan,
Xiaofang Xu
Affiliations
Zhenfang Du
Department of Genetic and Developmental Biology, School of Medicine, Southeast University, Nanjing 210003, China
Jinghan Sun
School of Life Science and Technology, Southeast University, Nanjing 210018, China
Yunkai Zhang
BioSpatula LLC, Telford, PA 18969, USA
Nigaerayi Hesilaiti
Department of Genetic and Developmental Biology, School of Medicine, Southeast University, Nanjing 210003, China
Qi Xia
Department of Genetic and Developmental Biology, School of Medicine, Southeast University, Nanjing 210003, China
Heqing Cui
Department of Radiotherapy, Nanjing Chest Hospital, Nanjing Medical University Affiliated Brain Hospital, Nanjing 210029, China
Na Fan
Department of Respiratory Medicine and Critical Care Medicine, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
Xiaofang Xu
Department of Thoracic Surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou 310022, China
Oncogenic mutations within the EGFR kinase domain are well-established driver mutations in non–small cell lung cancer (NSCLC). Small-molecule tyrosine kinase inhibitors (TKIs) specifically targeting these mutations have improved treatment outcomes for patients with this subtype of NSCLC. The selectivity of these targeted agents is based on the location of the mutations within the exons of the EGFR gene, and grouping mutations based on structural similarities has proved a useful tool for conceptualizing the heterogeneity of TKI response. Structure-based analysis of EGFR mutations has influenced TKI development, and improved structural understanding will inform continued therapeutic development and further improve patient outcomes. In this review, we summarize recent progress on targeted therapy strategies for patients with EGFR-mutant NSCLC based on structure and function analysis.
