Organoid profiling identifies common responders to chemotherapy in pancreatic cancer

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Organoid profiling identifies common responders to chemotherapy in pancreatic cancer
 
Tiriac, Hervé; Belleau, Pascal; Engle, Dannielle D.; Plenker, Dennis; Deschênes, Astrid; Somerville, Tim D.D.; Froeling, Fieke E.M.; Burkhart, Richard A.; Denroche, Robert E.; Jang, Gun Ho; Miyabayashi, Koji; Young, C. Megan; Patel, Hardik; Ma, Michelle; Lacomb, Joseph F.; Palmaira, Randze Lerie D.; Javed, Ammar A.; Huynh, Jasmine C.; Johnson, Molly; Arora, Kanika; Robine, Nicolas; Shah, Minita; Sanghvi, Rashesh; Goetz, Austin B.; Lowder, Cinthya Y.; Martello, Laura; Driehuis, Else; Lecomte, Nicolas; Askan, Gokce; Iacobuzio-Donahue, Christine A.; Clevers, Hans; Wood, Laura D.; Hruban, Ralph H.; Thompson, Elizabeth; Aguirre, Andrew J.; Wolpin, Brian M.; Sasson, Aaron; Kim, Joseph; Wu, Maoxin; Bucobo, Juan Carlos; Allen, Peter; Sejpal, Divyesh V.; Nealon, William; Sullivan, James D.; Winter, Jordan M.; Gimotty, Phyllis A.; Grem, Jean L.; Dimaio, Dominick J.; Buscaglia, Jonathan M.; Grandgenett, Paul M.; Brody, Jonathan R.; Hollingsworth, Michael A.; O’kane, Grainne M.; Notta, Faiyaz; Kim, Edward; Crawford, James M.; Devoe, Craig; Ocean, Allyson; Wolfgang, Christopher L.; Yu, Kenneth H.; Li, Ellen; Vakoc, Christopher R.; Hubert, Benjamin; Fischer, Sandra E.; Wilson, Julie M.; Moffitt, Richard; Knox, Jennifer; Krasnitz, Alexander; Gallinger, Steven; Tuveson, David A.
(2018) Cancer Discovery, volume 8, issue 9, pp. 1112 - 1129
(Article)
Abstract
Pancreatic cancer is the most lethal common solid malignancy. Systemic therapies are often ineffective, and predictive biomarkers to guide treatment are urgently needed. We generated a pancreatic cancer patient-derived organoid (PDO) library that recapitulates the mutational spectrum and transcriptional subtypes of primary pancreatic cancer. New driver oncogenes were nominated and ... read more
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Keywords: Antineoplastic Agents/pharmacology, Drug Resistance, Neoplasm/drug effects, Drug Screening Assays, Antitumor, Gene Expression Profiling/methods, Gene Expression Regulation, Neoplastic/drug effects, Gene Regulatory Networks/drug effects, Humans, Molecular Targeted Therapy, Organoids/chemistry, Pancreatic Neoplasms/drug therapy, Precision Medicine, Prospective Studies, Sequence Analysis, RNA, Standard of Care, Tumor Cells, Cultured, Oncology, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Journal Article, Research Support, N.I.H., Extramural
DOI: https://doi.org/10.1158/2159-8290.CD-18-0349
ISSN: 2159-8274
Publisher: American Association for Cancer Research Inc.
Note: Funding Information: We would like to thank the patients, families, and clinicians who contributed to this work. This work was supported by the Lustgarten Foundation (D.A. Tuveson). D.A. Tuveson is a distinguished scholar of the Lustgarten Foundation and Director of the Lustgarten Foundation Dedicated Laboratory of Pancreatic Cancer Research. S. Gallinger is supported by the Ontario Institute for Cancer Research, charitable donations from the Canadian Friends of the Hebrew University (Alex U. Soyka) and the Pancreatic Cancer Canada Foundation, and the Leb-ovich Chair in Hepatobiliary/Pancreatic Surgical Oncology. This project was also supported in part by the NCI/LEIDOS Human Cancer Models Initiative (HHSN26100008; D.A. Tuveson, H. Clevers, and J.M. Crawford), NIH 5P50CA101955-07 (D.A. Tuveson), P20CA192996-03 (D.A. Tuveson), 1U10CA180944-04 (D.A. Tuveson), 5U01CA168409-5 (D.A. Tuveson), 1R01CA188134-01 (D.A. Tuveson), 1R01CA190092-04 (D.A. Tuveson), 5T32CA148056 (D.D. Engle), 5K99CA204725 (D.D. Engle), 5P01CA013106 (C.R. Vakoc), 5P30CA45508 (D.A. Tuve-son and P.A. Gilmoty), 1R01CA212600-01 (J.R. Brody and J.M. Winter), P20CA192994 (E. Li), R01CA202762 (K.H. Yu), P50CA127297 (M.A. Hollingsworth; UNMC RAP), U01CA210240 (M.A. Hollings-worth, D.A. Tuveson; UNMC RAP), and 5R50CA211462 (M.A. Hol-lingsworth; UNMC RAP), V Foundation Translational Grant (K.H. Yu and D.A. Tuveson), Cold Spring Harbor Laboratory Association (D.A. Tuveson), Stand Up To Cancer/AACRPS09 (D.A. Tuveson), Precision Medicine Research Associates (D.A. Tuveson), SWOG ITSC 5U10CA180944-04 (D.A. Tuveson, H. Tiriac, and E.J. Kim), Pancreatic Cancer Action Network-AACR 16-20-25-VAKO (C.R.Vakoc), State of New York C150158 (T.D.D. Somerville; the opinions, results, findings, and/or interpretation of data contained herein are the responsibility of the authors and do not necessarily represent the opinions, interpretations or policy of New York State), Concetta Greenberg in memory of Marvin S. Greenberg, MD (J.R. Brody and J.M. Winter), RAN grant from the AACR Pancreatic Cancer Action Network (J.R. Brody and J.M. Winter), ASGE Endoscopic Research Award 71040 (J.M. Buscaglia), Simons Foundation Award 415604 (E. Li), and Canadian Cancer Society Research Institute grant 702316 (S. Gall-inger). We acknowledge the Cold Spring Harbor Laboratory Tissue Culture and Next Generation Sequencing Shared Resources, which are funded by NIH Cancer Center Support Grant 5P30CA045508. We also acknowledge the contributions of Production Sequencing, Genome Sequencing Informatics and Tissue Portal (Diagnostic Development) at the Ontario Institute for Cancer Research, as well as the University Health Network BioBank. The pancreatic cancer patient study (ICGC-CA, COMPASS) was conducted with the support of the Ontario Institute for Cancer Research (PanCuRx Translational Research Initiative) through funding provided by the Government of Ontario. Funding Information: We would like to thank the patients, families, and clinicians who contributed to this work. This work was supported by the Lustgarten Foundation (D.A. Tuveson). D.A. Tuveson is a distinguished scholar of the Lustgarten Foundation and Director of the Lustgarten Foundation Dedicated Laboratory of Pancreatic Cancer Research. S. Gallinger is supported by the Ontario Institute for Cancer Research, charitable donations from the Canadian Friends of the Hebrew University (Alex U. Soyka) and the Pancreatic Cancer Canada Foundation, and the Lebovich Chair in Hepatobiliary/Pancreatic Surgical Oncology. This project was also supported in part by the NCI/LEIDOS Human Cancer Models Initiative (HHSN26100008; D.A. Tuveson, H. Clevers, and J.M. Crawford), NIH5P50CA101955-07 (D.A. Tuveson), P20CA192996-03 (D.A. Tuveson), 1U10CA180944-04 (D.A. Tuveson), 5U01CA168409-5 (D.A. Tuveson), 1R01CA188134-01 (D.A. Tuveson), 1R01CA190092-04 (D.A. Tuveson), 5T32CA148056 (D.D. Engle), 5K99CA204725 (D.D. Engle), 5P01CA013106 (C.R. Vakoc), 5P30CA45508 (D.A. Tuveson and P.A. Gilmoty), 1R01CA212600-01 (J.R. Brody and J.M. Winter), P20CA192994 (E. Li), R01CA202762 (K.H. Yu), P50CA127297 (M.A. Hollingsworth; UNMC RAP), U01CA210240 (M.A. Hollingsworth, D.A. Tuveson; UNMC RAP), and 5R50CA211462 (M.A. Hollingsworth; UNMC RAP), V Foundation Translational Grant (K.H. Yu and D.A. Tuveson), Cold Spring Harbor Laboratory Association (D.A. Tuveson), Stand Up To Cancer/AACRPS09 (D.A. Tuveson), Precision Medicine Research Associates (D.A. Tuveson), SWOG ITSC 5U10CA180944-04 (D.A. Tuveson, H. Tiriac, and E.J. Kim), Pancreatic Cancer Action Network-AACR 16-20-25-VAKO (C.R.Vakoc), State of New York C150158 (T.D.D. Somerville; the opinions, results, findings, and/or interpretation of data contained herein are the responsibility of the authors and do not necessarily represent the opinions, interpretations or policy of New York State), Concetta Greenberg in memory of Marvin S. Greenberg, MD (J.R. Brody and J.M. Winter), RAN grant from the AACRPancreatic Cancer Action Network (J.R. Brody and J.M. Winter), ASGE Endoscopic Research Award 71040 (J.M. Buscaglia), Simons Foundation Award 415604 (E. Li), and Canadian Cancer Society Research Institute grant 702316 (S. Gallinger). We acknowledge the Cold Spring Harbor Laboratory Tissue Culture and Next Generation Sequencing Shared Resources, which are funded by NIH Cancer Center Support Grant 5P30CA045508. We also acknowledge the contributions of Production Sequencing, Genome Sequencing Informatics and Tissue Portal (Diagnostic Development) at the Ontario Institute for Cancer Research, as well as the University Health Network BioBank. The pancreatic cancer patient study (ICGC-CA, COMPASS) was conducted with the support of the Ontario Institute for Cancer Research (PanCuRx Translational Research Initiative) through funding provided by the Government of Ontario. Funding Information: L.D. Wood is a consultant/advisory board member for Personal Genome Diagnostics. R.H. Hruban is a board member for MyDiag-nostics and reports receiving royalties from UpToDate. B.M. Wolpin reports receiving a commercial research grant from Celgene. A. Sasson has ownership interest (including patents) in Sanguine Diagnostics and Therapeutics. C.R. Vakoc reports receiving a commercial research grant from Boehringer Ingelheim and is a consultant/advisory board member for KSQ Therapeutics. No potential conflicts of interest were disclosed by the other authors. Publisher Copyright: ©2018 American Association for Cancer Research.
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