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Personalized In Vitro and In Vivo Cancer Models to Guide Precision Medicine.

TitlePersonalized In Vitro and In Vivo Cancer Models to Guide Precision Medicine.
Publication TypeJournal Article
Year of Publication2017
AuthorsPauli C, Hopkins BD, Prandi D, Shaw R, Fedrizzi T, Sboner A, Sailer V, Augello M, Puca L, Rosati R, McNary TJ, Churakova Y, Cheung C, Triscott J, Pisapia D, Rao R, Mosquera JMiguel, Robinson B, Faltas BM, Emerling BE, Gadi VK, Bernard B, Elemento O, Beltran H, Demichelis F, Kemp CJ, Grandori C, Cantley LC, Rubin MA
JournalCancer Discov
Volume7
Issue5
Pagination462-477
Date Published2017 May
ISSN2159-8290
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. 456This article is highlighted in the In This Issue feature, p. 443.

DOI10.1158/2159-8290.CD-16-1154
Alternate JournalCancer Discov
PubMed ID28331002
PubMed Central IDPMC5413423
Grant ListR01 GM041890 / GM / NIGMS NIH HHS / United States
U54 CA132381 / CA / NCI NIH HHS / United States
U01 CA176303 / CA / NCI NIH HHS / United States
R01 CA116337 / CA / NCI NIH HHS / United States
U01 CA111275 / CA / NCI NIH HHS / United States

Weill Cornell Medicine
Cantley Lab
Weill Cornell Medical College Meyer Cancer Center
Belfer Research Building
413 E 69th St.
Room 1362, Box 50
New York, NY 10021 Phone: (646) 962-6297