TY - JOUR
T1 - A patient-derived explant (PDE) model of hormone-dependent cancer
AU - Centenera, Margaret M.
AU - Hickey, Theresa E.
AU - Jindal, Shalini
AU - Ryan, Natalie K.
AU - Ravindranathan, Preethi
AU - Mohammed, Hisham
AU - Robinson, Jessica L.
AU - Schiewer, Matthew J.
AU - Ma, Shihong
AU - Kapur, Payal
AU - Sutherland, Peter D.
AU - Hoffmann, Clive E.
AU - Roehrborn, Claus
AU - Gomella, Leonard G.
AU - Carroll, Jason S.
AU - Birrell, Stephen N.
AU - Knudsen, Karen E.
AU - Raj, Ganesh
AU - Butler, Lisa M.
AU - Tilley, Wayne D.
N1 - Funding Information:
We are grateful to all study participants, nurses, and pathologists who contributed their time and expertise to this project. We wish to thank all the surgeons who generously provided tissues. We also acknowledge the South Australian Coordinator of the Australian Prostate Cancer BioResource, Ms Pamela Saunders, who kindly assisted in the recruitment and collection of patient material and information. This work was supported by grants from the Movember Foundation (MRTA 3 to LMB and WDT), National Health and Medical Research Council of Australia (ID 627185 to LMB and WDT; ID 1008349 to LMB and WDT), Cancer Australia (ID 627229 to LMB and WDT; ID 1085471 to MMC and LMB; ID 1138766 to MMC and LMB), the Prostate Cancer Foundation of Australia (ID 2711 to LMB and MMC), the Royal Adelaide Hospital Research Committee (to MMC, LMB, and WDT), Susan G Komen for the Cure (ID BCTR0504475), the National Breast Cancer Foundation of Australia (ID NC-12-21), the Dorothy and James Cleo Thompson Foundation (to GVR), National Institutes of Health (R01 CA116777-05, R01 CA099996-09, and R01 ES016675-11 to KEK), the University of Cambridge Cancer Research UK (to JSC), the European Research Council (to JSC), and the European Molecular Biology Organization (to JSC). The Adelaide Prostate Cancer Centre is supported by an establishment grant from the Prostate Cancer Foundation of Australia (ID 2011/0452). MMC is a Prostate Cancer Foundation of Australia Young Investigator (ID YIG0412). LMB holds a senior research fellowship from the Australian Research Council. TEH holds a Postdoctoral Fellowship from the US Department of Defense Breast Cancer Research Program (W81XWH-11-1-0592). MJS holds a Predoctoral Fellowship from the United States Department of Defense (PC094195).
Publisher Copyright:
© 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.
PY - 2018/9
Y1 - 2018/9
N2 - Breast and prostate cancer research to date has largely been predicated on the use of cell lines in vitro or in vivo. These limitations have led to the development of more clinically relevant models, such as organoids or murine xenografts that utilize patient-derived material; however, issues related to low take rate, long duration of establishment, and the associated costs constrain use of these models. This study demonstrates that ex vivo culture of freshly resected breast and prostate tumor specimens obtained from surgery, termed patient-derived explants (PDEs), provides a high-throughput and cost-effective model that retains the native tissue architecture, microenvironment, cell viability, and key oncogenic drivers. The PDE model provides a unique approach for direct evaluation of drug responses on an individual patient's tumor, which is amenable to analysis using contemporary genomic technologies. The ability to rapidly evaluate drug efficacy in patient-derived material has high potential to facilitate implementation of personalized medicine approaches.
AB - Breast and prostate cancer research to date has largely been predicated on the use of cell lines in vitro or in vivo. These limitations have led to the development of more clinically relevant models, such as organoids or murine xenografts that utilize patient-derived material; however, issues related to low take rate, long duration of establishment, and the associated costs constrain use of these models. This study demonstrates that ex vivo culture of freshly resected breast and prostate tumor specimens obtained from surgery, termed patient-derived explants (PDEs), provides a high-throughput and cost-effective model that retains the native tissue architecture, microenvironment, cell viability, and key oncogenic drivers. The PDE model provides a unique approach for direct evaluation of drug responses on an individual patient's tumor, which is amenable to analysis using contemporary genomic technologies. The ability to rapidly evaluate drug efficacy in patient-derived material has high potential to facilitate implementation of personalized medicine approaches.
KW - ex vivo culture
KW - patient-derived explant
KW - preclinical tumor model
UR - http://www.scopus.com/inward/record.url?scp=85052398613&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85052398613&partnerID=8YFLogxK
U2 - 10.1002/1878-0261.12354
DO - 10.1002/1878-0261.12354
M3 - Article
C2 - 30117261
AN - SCOPUS:85052398613
SN - 1574-7891
VL - 12
SP - 1608
EP - 1622
JO - Molecular Oncology
JF - Molecular Oncology
IS - 9
ER -