作者
Hervé Tiriac, Pascal Belleau, Dannielle D Engle, Dennis Plenker, Astrid Deschênes, Tim DD Somerville, Fieke EM Froeling, Richard A Burkhart, Robert E Denroche, Gun-Ho Jang, Koji Miyabayashi, C Megan Young, Hardik Patel, Michelle Ma, Joseph F LaComb, Randze Lerie D Palmaira, Ammar A Javed, Jasmine C Huynh, Molly Johnson, Kanika Arora, Nicolas Robine, Minita Shah, Rashesh Sanghvi, Austin B Goetz, Cinthya Y Lowder, Laura Martello, Else Driehuis, Nicolas LeComte, Gokce Askan, Christine A Iacobuzio-Donahue, Hans Clevers, Laura D Wood, Ralph H Hruban, Elizabeth Thompson, Andrew J Aguirre, Brian M Wolpin, Aaron Sasson, Joseph Kim, Maoxin Wu, Juan Carlos Bucobo, Peter Allen, Divyesh V Sejpal, William Nealon, James D Sullivan, Jordan M Winter, Phyllis A Gimotty, Jean L Grem, Dominick J DiMaio, Jonathan M Buscaglia, Paul M Grandgenett, Jonathan R Brody, Michael A Hollingsworth, Grainne M O'Kane, Faiyaz Notta, Edward Kim, James M Crawford, Craig Devoe, Allyson Ocean, Christopher L Wolfgang, Kenneth H Yu, Ellen Li, Christopher R Vakoc, Benjamin Hubert, Sandra E Fischer, Julie M Wilson, Richard Moffitt, Jennifer Knox, Alexander Krasnitz, Steven Gallinger, David A Tuveson
发表日期
2018/9/1
期刊
Cancer discovery
卷号
8
期号
9
页码范围
1112-1129
出版商
American Association for Cancer Research
简介
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 …
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