Engineering perfusion to meet tumor biology: are vascularized tumor-on-a-chip models ready to drive therapy innovation?

Abstract

The development of effective cancer therapies remains constrained by the complex and dynamic nature of the tumor microenvironment (TME), with tumor vasculature representing a critical barrier and modulator of treatment response. This review critically examines recent advances in the generation of vascularized tumor models using organ-on-a-chip (OoC) microfluidic technologies, emphasizing their capacity to recapitulate key interactions between tumor cells, stroma, and vasculature in vitro. We outline the mechanistic roles of tumor vasculature in therapy resistance, metastatic dissemination, and immune modulation, and highlight current strategies targeting vasculature for improved therapeutic outcomes. State-of-the-art biomaterials and engineering approaches, including template-based fabrication, self-organization, and the integration of patient-derived organoids, are discussed regarding their efficacy in constructing physiologically relevant vasculature. The review critically assesses findings from drug testing studies and discusses the translational potential of microfluidic platform capabilities, such as real-time monitoring, precise flow control, and functional assessment of vessel permeability and drug delivery, while identifying key limitations for clinical implementation. Challenges in standardization, scalability, and clinical translation are discussed, and recommendations are proposed to enhance the human-relevance and impact of vascularized OoC models in preclinical oncology research. These advanced platforms represent a transformative approach for bridging the translational gap between preclinical research and clinical oncology, offering opportunities to advance personalized cancer therapeutics and improve patient outcomes.