High-Throughput Screening of Precision-Therapeutics in Patient-Derived Micro-Tumors Maintained under Physiological Conditions

Cancer is one of the leading causes of death worldwide with global medical costs totaling over $1.2 trillion/year. In spite of significant advances in our molecular understanding, diagnosis, and treatment over the last decade, complete tumor eradication is seldom achieved due in part to the persistence of stem cell-like tumor cells, termed cancer stem cells.

In this study, we establish a high throughput platform in which vascularized 3D tumor organoids are assembled in basement membrane with oxygen micro-sensors embedded in the tissue itself. Co-cultures of human hepatocellular carcinoma, HepG2, and microvascular endothelial cells formed organoids with diameter ranging from 300 to 800±50 µm. To monitor tumor oxygen consumption rates in real time, we utilized a specially designed OPAL system that measures fluorescent phase shift of ruthenium-based micro-beads. Automation of this system allows high-throughput screening of micro-tumors metabolism in response to exposure with FDA approved drugs. Micro-tumors can be formed from a patient’s biopsy, allowing clinicians to tailor the most efficient treatment with current available drugs on the market to the patient own tumor.

Therefore, the goal of this study is to build a platform that permits the high- throughput screening of precision-therapeutics in patient-derived micro-tumors maintained under physiological conditions. The novelty of our approach lies in the ability to continuously monitor the metabolic phenotype of cancer stem cells in their native microenvironment, elucidating strategies to eradicate the disease at its root.