Personalized Vascularized Tumor Organoid-on-a-Chip for Tumor Metastasis and Therapeutic Targeting Assessment

Abstract

While tumor organoids have revolutionized cancer research by recapitulating the cellular architecture and behaviors of real tumors in vitro, their lack of functional vasculature hinders their attainment of full physiological capabilities. Current efforts to vascularize organoids are struggling to achieve well-defined vascular networks, mimicking the intricate hierarchy observed in vivo, which restricts the physiological relevance particularly for studying tumor progression and response to therapies targeting the tumor vasculature. An innovative vascularized patient-derived tumor organoids (PDTOs)-on-a-chip with hierarchical, tumor-specific microvasculature is presented, providing a versatile platform to explore tumor-vascular dynamics and antivascular drug efficacy. It is found that highly metastatic tumor cells induced vessel angiogenesis and simultaneously migrated toward blood vessels via the Notch pathway. The evident association between the angiogenic and migratory capacities of PDTOs and their clinical metastatic outcomes underscores the potential of the innovative platform for evaluating tumor metastasis, thus offering valuable insights for clinical decision-making. Ultimately, the system represents a promising avenue for advancing the understanding of tumor metastasis and developing personalized treatment strategies based on patient-specific tumor characteristics.

Keywords: angiogenesis; microfluidics; organoids‐on‐a‐chip; tumor migration; tumor perivascular niche.