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Organoid Profiling Identifies Common Responders to Chemotherapy in Pancreatic Cancer.

Publication ,  Journal Article
Tiriac, H; Belleau, P; Engle, DD; Plenker, D; Deschênes, A; Somerville, TDD; Froeling, FEM; Burkhart, RA; Denroche, RE; Jang, G-H; Young, CM ...
Published in: Cancer Discov
September 2018

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. 1062This article is highlighted in the In This Issue feature, p. 1047.

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Published In

Cancer Discov

DOI

EISSN

2159-8290

Publication Date

September 2018

Volume

8

Issue

9

Start / End Page

1112 / 1129

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Standard of Care
  • Sequence Analysis, RNA
  • Prospective Studies
  • Precision Medicine
  • Pancreatic Neoplasms
  • Organoids
  • Molecular Targeted Therapy
  • Humans
  • Gene Regulatory Networks
 

Citation

APA
Chicago
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Tiriac, H., Belleau, P., Engle, D. D., Plenker, D., Deschênes, A., Somerville, T. D. D., … Tuveson, D. A. (2018). Organoid Profiling Identifies Common Responders to Chemotherapy in Pancreatic Cancer. Cancer Discov, 8(9), 1112–1129. https://doi.org/10.1158/2159-8290.CD-18-0349
Tiriac, Hervé, Pascal Belleau, Dannielle D. Engle, Dennis Plenker, Astrid Deschênes, Tim D. D. Somerville, Fieke E. M. Froeling, et al. “Organoid Profiling Identifies Common Responders to Chemotherapy in Pancreatic Cancer.Cancer Discov 8, no. 9 (September 2018): 1112–29. https://doi.org/10.1158/2159-8290.CD-18-0349.
Tiriac H, Belleau P, Engle DD, Plenker D, Deschênes A, Somerville TDD, et al. Organoid Profiling Identifies Common Responders to Chemotherapy in Pancreatic Cancer. Cancer Discov. 2018 Sep;8(9):1112–29.
Tiriac, Hervé, et al. “Organoid Profiling Identifies Common Responders to Chemotherapy in Pancreatic Cancer.Cancer Discov, vol. 8, no. 9, Sept. 2018, pp. 1112–29. Pubmed, doi:10.1158/2159-8290.CD-18-0349.
Tiriac H, Belleau P, Engle DD, Plenker D, Deschênes A, Somerville TDD, Froeling FEM, Burkhart RA, Denroche RE, Jang G-H, Miyabayashi K, Young CM, Patel H, Ma M, LaComb JF, Palmaira RLD, Javed AA, Huynh JC, Johnson M, Arora K, Robine N, Shah M, Sanghvi R, Goetz AB, Lowder CY, Martello L, Driehuis E, LeComte N, Askan G, Iacobuzio-Donahue CA, Clevers H, Wood LD, Hruban RH, Thompson E, Aguirre AJ, Wolpin BM, Sasson A, Kim J, Wu M, Bucobo JC, Allen P, Sejpal DV, Nealon W, Sullivan JD, Winter JM, Gimotty PA, Grem JL, DiMaio DJ, Buscaglia JM, Grandgenett PM, Brody JR, Hollingsworth MA, O’Kane GM, Notta F, Kim E, Crawford JM, Devoe C, Ocean A, Wolfgang CL, Yu KH, Li E, Vakoc CR, Hubert B, Fischer SE, Wilson JM, Moffitt R, Knox J, Krasnitz A, Gallinger S, Tuveson DA. Organoid Profiling Identifies Common Responders to Chemotherapy in Pancreatic Cancer. Cancer Discov. 2018 Sep;8(9):1112–1129.

Published In

Cancer Discov

DOI

EISSN

2159-8290

Publication Date

September 2018

Volume

8

Issue

9

Start / End Page

1112 / 1129

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Standard of Care
  • Sequence Analysis, RNA
  • Prospective Studies
  • Precision Medicine
  • Pancreatic Neoplasms
  • Organoids
  • Molecular Targeted Therapy
  • Humans
  • Gene Regulatory Networks