Applications and challenges of Drosophila melanogaster as a laboratory model in human cancer research: a narrative review

Abstract

INTRODUCTION: Drosophila melanogaster, a well-established model organism in biomedical research, has significantly advanced our understanding of genetic mechanisms underlying human diseases. Its genetic similarity to humans, with approximately 75% of human disease-related genes having orthologues in the fly genome, renders it a valuable tool for studying complex conditions like cancer. The organism's low cost, short life cycle, and manipulable genome make it ideal for high-throughput studies. MAIN TEXT: Recent advances have enabled the use of Drosophila as a model for different cancer types, including colorectal, thyroid, lung, and brain cancers. These models replicate key tumor characteristics such as cell proliferation, invasion, and metastasis. Drosophila's utility in drug screening has been exemplified through heterochromatin-promoting assays and personalized medicine approaches using patient-specific gene expression data. Its role in testing therapeutic combinations, such as MEK inhibitors with statins for lung cancer, underscores its translational potential. Despite its utility, the model has notable limitations. Differences in tumor biology between flies and humans, especially regarding organ systems and immune responses, limit its applicability in certain cancer types and metastatic studies. Furthermore, environmental influences and the simplified genetic background of Drosophila may not accurately represent human cancer complexity. Ethical concerns and translational challenges also exist, warranting cautious interpretation of results. The recent advancements in CRISPR-based genome editing, particularly cytosine and adenine base editors, have improved gene-editing efficiency in Drosophila, supporting its ongoing use in precision oncology. Future directions point toward integrating Drosophila models with other in vivo and in silico systems to optimize personalized drug discovery and better emulate human tumor heterogeneity. CONCLUSION: While the use of Drosophila melanogaster has intrinsic limitations, its genetic tractability and compatibility with cutting-edge genomic tools position it as a complementary model to mammalian systems. Continued innovations in genetic engineering and model integration will further strengthen its role in translational oncology and precision medicine. This review explores the applications of the model in human cancer research and highlights the major challenges with its use. This is crucial for the fight against cancer, as it helps inform researchers of the potential areas that require further research, especially with the rapid evolution of personalised medicine.