RT Journal Article
SR Electronic
T1 Organoid Profiling Identifies Common Responders to Chemotherapy in Pancreatic Cancer
JF Cancer Discovery
JO Cancer Discov
FD American Association for Cancer Research
SP 1112
OP 1129
DO 10.1158/2159-8290.CD-18-0349
VO 8
IS 9
A1 Tiriac, Hervé
A1 Belleau, Pascal
A1 Engle, Dannielle D.
A1 Plenker, Dennis
A1 Deschênes, Astrid
A1 Somerville, Tim D. D.
A1 Froeling, Fieke E. M.
A1 Burkhart, Richard A.
A1 Denroche, Robert E.
A1 Jang, Gun-Ho
A1 Miyabayashi, Koji
A1 Young, C. Megan
A1 Patel, Hardik
A1 Ma, Michelle
A1 LaComb, Joseph F.
A1 Palmaira, Randze Lerie D.
A1 Javed, Ammar A.
A1 Huynh, Jasmine C.
A1 Johnson, Molly
A1 Arora, Kanika
A1 Robine, Nicolas
A1 Shah, Minita
A1 Sanghvi, Rashesh
A1 Goetz, Austin B.
A1 Lowder, Cinthya Y.
A1 Martello, Laura
A1 Driehuis, Else
A1 LeComte, Nicolas
A1 Askan, Gokce
A1 Iacobuzio-Donahue, Christine A.
A1 Clevers, Hans
A1 Wood, Laura D.
A1 Hruban, Ralph H.
A1 Thompson, Elizabeth
A1 Aguirre, Andrew J.
A1 Wolpin, Brian M.
A1 Sasson, Aaron
A1 Kim, Joseph
A1 Wu, Maoxin
A1 Bucobo, Juan Carlos
A1 Allen, Peter
A1 Sejpal, Divyesh V.
A1 Nealon, William
A1 Sullivan, James D.
A1 Winter, Jordan M.
A1 Gimotty, Phyllis A.
A1 Grem, Jean L.
A1 DiMaio, Dominick J.
A1 Buscaglia, Jonathan M.
A1 Grandgenett, Paul M.
A1 Brody, Jonathan R.
A1 Hollingsworth, Michael A.
A1 O'Kane, Grainne M.
A1 Notta, Faiyaz
A1 Kim, Edward
A1 Crawford, James M.
A1 Devoe, Craig
A1 Ocean, Allyson
A1 Wolfgang, Christopher L.
A1 Yu, Kenneth H.
A1 Li, Ellen
A1 Vakoc, Christopher R.
A1 Hubert, Benjamin
A1 Fischer, Sandra E.
A1 Wilson, Julie M.
A1 Moffitt, Richard
A1 Knox, Jennifer
A1 Krasnitz, Alexander
A1 Gallinger, Steven
A1 Tuveson, David A.
YR 2018
UL http://cancerdiscovery.aacrjournals.org/content/8/9/1112.abstract
AB 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 transcriptomic analyses revealed unique clusters. PDOs exhibited heterogeneous responses to standard-of-care chemotherapeutics and investigational agents. In a case study manner, we found that PDO therapeutic profiles paralleled patient outcomes and that PDOs enabled longitudinal assessment of chemosensitivity and evaluation of synchronous metastases. We derived organoid-based gene expression signatures of chemosensitivity that predicted improved responses for many patients to chemotherapy in both the adjuvant and advanced disease settings. Finally, we nominated alternative treatment strategies for chemorefractory PDOs using targeted agent therapeutic profiling. We propose that combined molecular and therapeutic profiling of PDOs may predict clinical response and enable prospective therapeutic selection.Significance: New approaches to prioritize treatment strategies are urgently needed to improve survival and quality of life for patients with pancreatic cancer. Combined genomic, transcriptomic, and therapeutic profiling of PDOs can identify molecular and functional subtypes of pancreatic cancer, predict therapeutic responses, and facilitate precision medicine for patients with pancreatic cancer. Cancer Discov; 8(9); 1112–29. ©2018 AACR.See related commentary by Collisson, p. 1062.This article is highlighted in the In This Issue feature, p. 1047