Personalized <i>In Vitro</i> and <i>In Vivo</i> Cancer Models to Guide Precision Medicine

TLDR

Precision medicine tailors interventions based on genes, environment, and lifestyle, and integrating genomic data with drug screening from personalized in vitro and in vivo cancer models advances precision cancer care. The study develops a precision cancer care platform that combines whole‑exome sequencing with a living biobank for high‑throughput drug screening on patient‑derived tumor organoids. The platform uses whole‑exome sequencing linked to a living biobank and high‑throughput drug screening to identify effective treatment strategies. The platform has established 56 organoid cultures and 19 PDX models from 769 trial patients, identified effective drugs and combinations in four cases that were validated in 3‑D cultures and PDX models, and enables novel therapeutic approaches for patients lacking standard options. Published in Cancer Discovery 7(5):462–477; ©2017 AACR; see commentary by Picco and Garnett, p.456, and highlighted in the In This Issue feature, p.443.

Abstract

Abstract Precision medicine is an approach that takes into account the influence of individuals' genes, environment, and lifestyle exposures to tailor interventions. Here, we describe the development of a robust precision cancer care platform that integrates whole-exome sequencing with a living biobank that enables high-throughput drug screens on patient-derived tumor organoids. To date, 56 tumor-derived organoid cultures and 19 patient-derived xenograft (PDX) models have been established from the 769 patients enrolled in an Institutional Review Board–approved clinical trial. Because genomics alone was insufficient to identify therapeutic options for the majority of patients with advanced disease, we used high-throughput drug screening to discover effective treatment strategies. Analysis of tumor-derived cells from four cases, two uterine malignancies and two colon cancers, identified effective drugs and drug combinations that were subsequently validated using 3-D cultures and PDX models. This platform thereby promotes the discovery of novel therapeutic approaches that can be assessed in clinical trials and provides personalized therapeutic options for individual patients where standard clinical options have been exhausted. Significance: Integration of genomic data with drug screening from personalized in vitro and in vivo cancer models guides precision cancer care and fuels next-generation research. Cancer Discov; 7(5); 462–77. ©2017 AACR. See related commentary by Picco and Garnett, p. 456. This article is highlighted in the In This Issue feature, p. 443