PersonalizedIn VitroandIn VivoCancer Models to Guide Precision Medicine.
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 personalizedin vitroandin vivocancer 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.
Englander Institute for Precision Medicine, Weill Cornell Medicine-New York Presbyterian Hospital, New York, New York.|Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York.|Institute of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.
Chantal
C
Pauli
Meyer Cancer Center, Weill Cornell Medicine, New York, New York.
Benjamin D
BD
Hopkins
Center for Integrative Biology, University of Trento, Trento, Italy.
Davide
D
Prandi
Cure First and SEngine Precision Medicine, Seattle, Washington.
Reid
R
Shaw
Center for Integrative Biology, University of Trento, Trento, Italy.
Tarcisio
T
Fedrizzi
Englander Institute for Precision Medicine, Weill Cornell Medicine-New York Presbyterian Hospital, New York, New York.|Meyer Cancer Center, Weill Cornell Medicine, New York, New York.|Institute for Computational Biomedicine, Weill Cornell Medicine, New York, New York.
Andrea
A
Sboner
Englander Institute for Precision Medicine, Weill Cornell Medicine-New York Presbyterian Hospital, New York, New York.|Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York.
Verena
V
Sailer
Englander Institute for Precision Medicine, Weill Cornell Medicine-New York Presbyterian Hospital, New York, New York.|Meyer Cancer Center, Weill Cornell Medicine, New York, New York.
Michael
M
Augello
Englander Institute for Precision Medicine, Weill Cornell Medicine-New York Presbyterian Hospital, New York, New York.
Loredana
L
Puca
Cure First and SEngine Precision Medicine, Seattle, Washington.
Rachele
R
Rosati
Englander Institute for Precision Medicine, Weill Cornell Medicine-New York Presbyterian Hospital, New York, New York.
Terra J
TJ
McNary
Englander Institute for Precision Medicine, Weill Cornell Medicine-New York Presbyterian Hospital, New York, New York.
Yelena
Y
Churakova
Englander Institute for Precision Medicine, Weill Cornell Medicine-New York Presbyterian Hospital, New York, New York.
Cynthia
C
Cheung
Englander Institute for Precision Medicine, Weill Cornell Medicine-New York Presbyterian Hospital, New York, New York.
Joanna
J
Triscott
Englander Institute for Precision Medicine, Weill Cornell Medicine-New York Presbyterian Hospital, New York, New York.|Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York.
David
D
Pisapia
Englander Institute for Precision Medicine, Weill Cornell Medicine-New York Presbyterian Hospital, New York, New York.|Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York.
Rema
R
Rao
Englander Institute for Precision Medicine, Weill Cornell Medicine-New York Presbyterian Hospital, New York, New York.|Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York.
Juan Miguel
JM
Mosquera
Englander Institute for Precision Medicine, Weill Cornell Medicine-New York Presbyterian Hospital, New York, New York.|Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York.
Brian
B
Robinson
Englander Institute for Precision Medicine, Weill Cornell Medicine-New York Presbyterian Hospital, New York, New York.|Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, New York.
Bishoy M
BM
Faltas
Meyer Cancer Center, Weill Cornell Medicine, New York, New York.
Brooke E
BE
Emerling
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Vijayakrishna K
VK
Gadi
Cure First and SEngine Precision Medicine, Seattle, Washington.
Brady
B
Bernard
Englander Institute for Precision Medicine, Weill Cornell Medicine-New York Presbyterian Hospital, New York, New York.|Meyer Cancer Center, Weill Cornell Medicine, New York, New York.|Institute for Computational Biomedicine, Weill Cornell Medicine, New York, New York.
Olivier
O
Elemento
Englander Institute for Precision Medicine, Weill Cornell Medicine-New York Presbyterian Hospital, New York, New York.|Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, New York.
Himisha
H
Beltran
Englander Institute for Precision Medicine, Weill Cornell Medicine-New York Presbyterian Hospital, New York, New York.|Center for Integrative Biology, University of Trento, Trento, Italy.
Francesca
F
Demichelis
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Christopher J
CJ
Kemp
Cure First and SEngine Precision Medicine, Seattle, Washington.
Carla
C
Grandori
Meyer Cancer Center, Weill Cornell Medicine, New York, New York.
Lewis C
LC
Cantley
Englander Institute for Precision Medicine, Weill Cornell Medicine-New York Presbyterian Hospital, New York, New York. rubinma@med.cornell.edu.|Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York.|Meyer Cancer Center, Weill Cornell Medicine, New York, New York.
Mark A
MA
Rubin
D000818:Animals; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D006801:Humans; D051379:Mice; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics; D009940:Organoids; D057285:Precision Medicine / Q000379:methods*; D000073359:Exome Sequencing / Q000379:methods*; D023041:Xenograft Model Antitumor Assays