UCLA

Precision medicine has the potential to revolutionize cancer care by identifying promising treatment strategies specific to each patient’s disease. While advances in genome sequencing have facilitated the identification of mutations within tumors, only a small number of strict relationships between gene alterations and drug response have been established. Functional precision medicine is an emerging paradigm that exposes living patient-derived tissue to drugs to observe response. The work presented in this thesis will describe the development and implementation of high-throughput platforms for organoid screening. First, I will discuss the varied approaches that have been used to model tumors in vitro. Then, I will present our findings from screening organoids derived from 127 patients with sarcoma specimens collected at UCLA. Next, I describe the development of a pipeline for screening bioprinted organoids with high-speed live cell interferometry to enhance consistency and assess response to treatment with single-organoid resolution. Finally, I will detail the development of new methods for screening radiotherapy and liver-metabolized prodrugs on tumor organoids. This work contributes to the overall goal of creating robust, automated, and informative organoid screening pipelines for the implementation of functional precision medicine in clinical oncology.