Lab-on-a-chip (LoC) technologies have emerged as transformative tools in cancer research, particularly in evaluating drug resistance, which remains a significant barrier to effective treatment. These miniaturized platforms allow for the integration of multiple laboratory functions onto a single chip, facilitating high-throughput screening and real-time monitoring of cellular responses to therapeutic agents. Despite their potential, several challenges hinder the widespread adoption of LoC systems in clinical settings. Key issues include the complexity of accurately replicating the tumor microenvironment (TME), which is critical for understanding cancer biology and drug interactions. Additionally, variability in chip design and fabrication raises concerns about standardization and reproducibility of results, complicating comparisons across studies. The integration of LoC technologies into clinical practice is further complicated by the need for translation from laboratory findings to patient-specific applications. High costs associated with advanced microfabrication techniques and the requirement for specialized technical expertise also limit accessibility for many researchers and clinicians. However, the future perspectives for LoC technologies are promising. Advancements in three-dimensional (3D) bioprinting and tissue engineering are expected to enhance TME modeling, while patient-derived tumor spheroids (PDTS) integrated into LoC platforms could facilitate personalized medicine approaches. Coupling LoC systems with omics technologies will provide deeper insights into the molecular mechanisms of drug resistance and help identify novel biomarkers. Furthermore, the integration of artificial intelligence and nanotechnology with LoC platforms has significantly enhanced their diagnostic accuracy, automation, and potential for personalized cancer treatment. As regulatory bodies increasingly accept LoC technologies as viable preclinical models, their integration into pharmaceutical development pipelines is likely to accelerate. This review aims to explore these challenges and future perspectives, highlighting the potential of LoC technologies in advancing cancer treatment paradigms. By examining the innovative applications of LoC systems, we aim to highlight their potential for enhancing our understanding of the complex interactions within the TME and their implications for personalized medicine. Additionally, it seeks to identify and discuss the key challenges that currently limit the widespread adoption of LoC technologies in clinical settings, including issues related to model complexity, standardization, and integration into existing drug development pipelines.
