Microfluidic Tissue Array Platform for Personalized Drug Screening Using Tumor Explants or Biopsies
Despite major improvements in molecular characterization of breast cancer, current biomarkers still fall short in accurate treatment prediction. Interrogating tumor tissue ex-vivo in its native conformation is a direct strategy for guiding treatment of individual patients but presents a challenge. In this study, we developed a microfluidic tissue array (FTA) using small biopsy samples (< 1mm3) mimicking physiological flow for consistent exchange of nutrients and waste, retaining the tumor native stroma. Cell/patient-derived breast cancer xenograft tissues were maintained over 2 weeks in the array and their response to therapeutic agents, doxorubicin or neratinib, were interrogated. Drug response in the uFTA showed >2-fold reduction in tumor cell viability which corroborated tumor size shrinkage in mice bearing the same tumor load. EdU/Ki67 assays indicated selective retention of cells with higher proliferative capacity after drug treatment, underscoring in vivo clinical relevance . We have also developed a valved-FTA to increase throughput and variety of treatment conditions on the same chip. Together, this FTA can be staged as a powerful, low-cost benchtop theranostic tool for personalized cancer therapeutics compatible with FDAs New Approach Methods.