Personalized in vitro and in vivo cancer models to guide precision medicine

Chantal Pauli, Benjamin D. Hopkins, Davide Prandi, Reid Shaw, Tarcisio Fedrizzi, Andrea Sboner, Verena Sailer, Michael Augello, Loredana Puca, Rachele Rosati, Terra J. McNary, Yelena Churakova, Cynthia Cheung, Joanna Triscott, David Pisapia, Rema Rao, Juan Miguel Mosquera, Brian Robinson, Bishoy M. Faltas, Brooke E. EmerlingVijayakrishna K. Gadi, Brady Bernard, Olivier Elemento, Himisha Beltran, Francesca Demichelis, Christopher J. Kemp, Carla Grandori, Lewis C. Cantley, Mark A. Rubin

Research output: Contribution to journalArticlepeer-review

339 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)462-477
Number of pages16
JournalCancer discovery
Volume7
Issue number5
DOIs
StatePublished - May 2017
Externally publishedYes

ASJC Scopus subject areas

  • Oncology

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