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