Lung cancer (LC) accounts for 18% of all cancer-related deaths worldwide and is a significant burden on public health [1]. LC is broadly classified into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Over the last 10 years, with the emergence of molecular genetic testing, including the detection of EGFR, BRAF, and MET mutations as well as ALK, ROS1, RET, and NTRK translocations, kinase inhibitors have significantly improved the overall survival of patients with NSCLC [2]. Additionally, immune checkpoint inhibitors have shown significant benefits as first- or second-line therapies for patients with advanced NSCLC, gradually expanding to stage II–III diseases. In extensive-stage SCLC, immune checkpoint inhibitors can be used as first-line treatments combined with platinum chemotherapy [3]. Despite revolutionary breakthroughs in targeted therapy and immunotherapy, the intermediate and advanced 5-year survival rates of only 10–20% remain discouraging [4]. Animal models play a crucial role in understanding disease biology and formulating successful diagnostic and treatment strategies for LC. Although genetically engineered and immunocompromised xenografted mice are commonly used vertebrate models, they have inherent limitations, including time and cost constraints. Recently, zebrafish have emerged as an attractive model organism for LC research, providing advantages such as high fecundity, optical translucency, and affordability ^[5][6][5,6]. Zebrafish models have been instrumental in investigating tumor mechanisms related to proliferation, metastasis, and angiogenesis, as well as providing a high-throughput platform for assessing the safety and efficacy of anticancer drugs. They can also be used to study the tumor microenvironment (TME) and personalized therapy.

In the late 1980s, zebrafish were introduced into laboratories for the first time for studying genetic and vertebrate development ^[7][39] and rapidly gained popularity in various disciplines of biology as an excellent model organism for human diseases. Their homologous brain structures, which are similar to those in mammals, and available sophisticated behavioral tests make zebrafish an effective tool for elucidating mechanisms of neurological and psychiatric disorders, including epilepsy, neurodegenerative disorders, affective disorders, schizophrenia, hyperactivity disorders, and drug-related disorders, as well as for drug discovery ^[8][40]. In cardiovascular research, zebrafish models have been proven comparable to mammalian ones with respect to the histology and electrophysiology of the heart, enabling the study of congenital heart defects, cardiomyopathy, and conduction disorders ^[9][41]. Similarly, zebrafish are valuable for studying vascular diseases involving endothelial dysfunction, atherosclerosis, and vascular aging, as vessel formation and remodeling processes are well-conserved ^[10][42]. In the field of hepatology, the significant homology between zebrafish and mammalian livers at the cellular level enables the investigation of genetic liver disorders, fatty liver, and liver cancer. The expression of cytochrome P450 enzymes, which metabolize xenobiotic compounds similarly to those in mammals, makes zebrafish valuable for evaluating drug hepatotoxicity and screening potential hepatoprotective compounds, thereby providing insights into toxicology and drug metabolism ^[11][43]. Additionally, zebrafish genetic tractability and cone-rich retinas provide unique opportunities to model various photoreceptor diseases ^[12][44], and zebrafish models of ocular coloboma have contributed to our understanding of the optic fissure morphogenesis and associated eye and lens defects ^[13][45]. Available ophthalmological tools, such as electroretinography and optical coherence tomography, further enhance the suitability of zebrafish for retinal assessment ^[12][44]. Zebrafish can be infected with many pathogenic microorganisms, including bacteria, viruses, Mycoplasma, and chlamydia ^[14][15][16][46,47,48]. For instance, zebrafish models of severe acute respiratory syndrome coronavirus 2, using an injection of the virus or viral antigens, have been developed that. These models are invaluable for studying host immune responses, vaccine mechanisms, potential side effects, and increased susceptibility of the elderly to COVID-19 infection ^[17][49]. Furthermore, zebrafish-based research on non-pathogenic microorganisms, such as gut microbiome, is flourishing ^[18][50]. Overall, zebrafish models have been demonstrated to be versatile and valuable tools for scientific research across various disciplines, providing insights into fundamental biological processes and advancing our understanding of human diseases.