Applications and Complementarity of Organ‐Chips and Animal Models in Lung Cancer Driver Gene Research

Alterations in driver genes in lung cancer, such as those in EGFR, KRAS, EML4-ALK, and TP53, play pivotal roles in tumor progression, therapeutic response, and resistance development. Therefore, it is important to develop research models that reflect both human tumor characteristics and systemic physiological responses. This review summarizes and compares previous studies of the application and complementarity of organ-chip technologies (including organoids and lung-on-a-chip) and traditional animal models (genetically engineered mouse models and patient-derived xenografts) for investigating the same genetic alterations. Existing literature demonstrates that animal models are well-suited for studying long-term tumor evolution and metastasis because of their intact immune systems, physiological environments, and immune-based therapies. However, organ-chips can rapidly establish models in controllable microenvironments, enabling the high-throughput screening of drugs and analyses of resistance mechanisms. Although both approaches demonstrate consistent trends in oncogenic potential and drug sensitivity across multiple genetic alterations, they differ in terms of time efficiency, microenvironmental control, and the capacity to recapitulate systemic responses. Thus, the two platforms may be complementary in preclinical lung cancer research, and their combined application may enhance the accuracy of gene function validation, drug efficacy evaluation, and clinical translation.