X-ray on chip: Quantifying therapeutic synergies between radiotherapy and anticancer drugs using soft tissue sarcoma tumor spheroids

Highlights: • Development of a microfluidic system to evaluate candidate drugs with clinical radiotherapy on tumor spheroids. • The orthovoltage-based irradiation technique enabled the delivery of four different radiation doses on one microfluidic system. • A synergistic effect of Talazoparib with radiotherapy on soft tissue sarcoma spheroids was demonstrated with clonogenic assays. • This tool lays the basis for the systemic search of molecular agent/radiotherapy synergies. Radioresistance, tumor microenvironment, and normal tissue toxicity from radiation limit the efficacy of radiotherapy in treating cancers. These challenges can be tackled by the discovery of new radiosensitizing and radioprotecting agents aimed at increasing the therapeutic efficacy of radiotherapy. The goal of this work was to develop a miniaturized microfluidic platform for the discovery of drugs that could be used in combination with radiotherapy. The microfluidic system will allow the toxicity testing of cancer spheroids to different combinations of radiotherapy and molecular agents.