Targeting the Tumor Microenvironment in EGFR-Mutant Lung Cancer: Opportunities and Challenges
Jeong Uk Lim,
Junyang Jung,
Yeon Wook Kim,
Chi Young Kim,
Sang Hoon Lee,
Dong Won Park,
Sue In Choi,
Wonjun Ji,
Chang Dong Yeo,
Seung Hyeun Lee
Affiliations
Jeong Uk Lim
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
Junyang Jung
Department of Anatomy and Neurobiology, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
Yeon Wook Kim
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea
Chi Young Kim
Division of Pulmonology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
Sang Hoon Lee
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Institute of Chest Diseases, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
Dong Won Park
Division of Pulmonary Medicine and Allergy, Department of Internal Medicine, Hanyang University College of Medicine, Seoul 04763, Republic of Korea
Sue In Choi
Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University College of Medicine, Seoul 02841, Republic of Korea
Wonjun Ji
Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 44610, Republic of Korea
Chang Dong Yeo
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 03083, Republic of Korea
Seung Hyeun Lee
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
Tyrosine kinase inhibitors (TKIs) have transformed the treatment of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer. However, treatment resistance remains a major challenge in clinical practice. The tumor microenvironment (TME) is a complex system composed of tumor cells, immune and non-immune cells, and non-cellular components. Evidence indicates that dynamic changes in TME during TKI treatment are associated with the development of resistance. Research has focused on identifying how each component of the TME interacts with tumors and TKIs to understand therapeutic targets that could address TKI resistance. In this review, we describe how TME components, such as immune cells, fibroblasts, blood vessels, immune checkpoint proteins, and cytokines, interact with EGFR-mutant tumors and how they can promote resistance to TKIs. Furthermore, we discuss potential strategies targeting TME as a novel therapeutic approach.
