The Promises and Challenges of Patient-derived Tumor Organoids in Drug Development and Precision Oncology

Overview

Journal Animal Model Exp Med

Date 2019 Nov 28

PMID 31773090

Citations 21

Authors

Lauren M Granat

Ooha Kambhampati

Stephanie Klosek

Brian Niedzwecki

Kian Parsa

Dong Zhang

Affiliations

Soon will be listed here.

Abstract

In the era of precision medicine, cancer researchers and oncologists are eagerly searching for more realistic, cost effective, and timely tumor models to aid drug development and precision oncology. Tumor models that can faithfully recapitulate the histological and molecular characteristics of various human tumors will be extremely valuable in increasing the successful rate of oncology drug development and discovering the most efficacious treatment regimen for cancer patients. Two-dimensional (2D) cultured cancer cell lines, genetically engineered mouse tumor (GEMT) models, and patient-derived tumor xenograft (PDTX) models have been widely used to investigate the biology of various types of cancers and test the efficacy of oncology drug candidates. However, due to either the failure to faithfully recapitulate the complexity of patient tumors in the case of 2D cultured cancer cells, or high cost and untimely for drug screening and testing in the case of GEMT and PDTX, new tumor models are urgently needed. The recently developed patient-derived tumor organoids (PDTO) offer great potentials in uncovering novel biology of cancer development, accelerating the discovery of oncology drugs, and individualizing the treatment of cancers. In this review, we will summarize the recent progress in utilizing PDTO for oncology drug discovery. In addition, we will discuss the potentials and limitations of the current PDTO tumor models.

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References

Votanopoulos K, Mazzocchi A, Sivakumar H, Forsythe S, Aleman J, Levine E . Appendiceal Cancer Patient-Specific Tumor Organoid Model for Predicting Chemotherapy Efficacy Prior to Initiation of Treatment: A Feasibility Study. Ann Surg Oncol. 2018; 26(1):139-147. PMC: 7992871. DOI: 10.1245/s10434-018-7008-2. View

Ravi M, Ramesh A, Pattabhi A . Contributions of 3D Cell Cultures for Cancer Research. J Cell Physiol. 2016; 232(10):2679-2697. DOI: 10.1002/jcp.25664. View

Tiriac H, Belleau P, Engle D, Plenker D, Deschenes A, Somerville T . Organoid Profiling Identifies Common Responders to Chemotherapy in Pancreatic Cancer. Cancer Discov. 2018; 8(9):1112-1129. PMC: 6125219. DOI: 10.1158/2159-8290.CD-18-0349. View

Rossi G, Manfrin A, Lutolf M . Progress and potential in organoid research. Nat Rev Genet. 2018; 19(11):671-687. DOI: 10.1038/s41576-018-0051-9. View

Bredenoord A, Clevers H, Knoblich J . Human tissues in a dish: The research and ethical implications of organoid technology. Science. 2017; 355(6322). DOI: 10.1126/science.aaf9414. View

Kersten K, de Visser K, van Miltenburg M, Jonkers J . Genetically engineered mouse models in oncology research and cancer medicine. EMBO Mol Med. 2016; 9(2):137-153. PMC: 5286388. DOI: 10.15252/emmm.201606857. View

Broutier L, Mastrogiovanni G, Verstegen M, Francies H, Morrill Gavarro L, Bradshaw C . Human primary liver cancer-derived organoid cultures for disease modeling and drug screening. Nat Med. 2017; 23(12):1424-1435. PMC: 5722201. DOI: 10.1038/nm.4438. View

Gao D, Vela I, Sboner A, Iaquinta P, Karthaus W, Gopalan A . Organoid cultures derived from patients with advanced prostate cancer. Cell. 2014; 159(1):176-187. PMC: 4237931. DOI: 10.1016/j.cell.2014.08.016. View

Buzzelli J, Ouaret D, Brown G, Allen P, Muschel R . Colorectal cancer liver metastases organoids retain characteristics of original tumor and acquire chemotherapy resistance. Stem Cell Res. 2018; 27:109-120. PMC: 5842239. DOI: 10.1016/j.scr.2018.01.016. View

10.

Lee S, Hu W, Matulay J, Silva M, Owczarek T, Kim K . Tumor Evolution and Drug Response in Patient-Derived Organoid Models of Bladder Cancer. Cell. 2018; 173(2):515-528.e17. PMC: 5890941. DOI: 10.1016/j.cell.2018.03.017. View

11.

Granat L, Kambhampati O, Klosek S, Niedzwecki B, Parsa K, Zhang D . The promises and challenges of patient-derived tumor organoids in drug development and precision oncology. Animal Model Exp Med. 2019; 2(3):150-161. PMC: 6762043. DOI: 10.1002/ame2.12077. View

12.

Shah M, Power D, Kindler H, Holen K, Kemeny M, Ilson D . A multicenter, phase II study of bortezomib (PS-341) in patients with unresectable or metastatic gastric and gastroesophageal junction adenocarcinoma. Invest New Drugs. 2010; 29(6):1475-81. DOI: 10.1007/s10637-010-9474-7. View

13.

Sato T, Vries R, Snippert H, van de Wetering M, Barker N, Stange D . Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature. 2009; 459(7244):262-5. DOI: 10.1038/nature07935. View

14.

Ratjen F . Cystic fibrosis: pathogenesis and future treatment strategies. Respir Care. 2009; 54(5):595-605. DOI: 10.4187/aarc0427. View

15.

SCHERER W, SYVERTON J, GEY G . Studies on the propagation in vitro of poliomyelitis viruses. IV. Viral multiplication in a stable strain of human malignant epithelial cells (strain HeLa) derived from an epidermoid carcinoma of the cervix. J Exp Med. 1953; 97(5):695-710. PMC: 2136303. DOI: 10.1084/jem.97.5.695. View

16.

Dinney C, McConkey D, Millikan R, Wu X, Bar-Eli M, Adam L . Focus on bladder cancer. Cancer Cell. 2004; 6(2):111-6. DOI: 10.1016/j.ccr.2004.08.002. View

17.

Jin K, Teng L, Shen Y, He K, Xu Z, Li G . Patient-derived human tumour tissue xenografts in immunodeficient mice: a systematic review. Clin Transl Oncol. 2010; 12(7):473-80. DOI: 10.1007/s12094-010-0540-6. View

18.

Siegel R, Miller K, Jemal A . Cancer statistics, 2019. CA Cancer J Clin. 2019; 69(1):7-34. DOI: 10.3322/caac.21551. View

19.

Li X, Francies H, Secrier M, Perner J, Miremadi A, Galeano-Dalmau N . Organoid cultures recapitulate esophageal adenocarcinoma heterogeneity providing a model for clonality studies and precision therapeutics. Nat Commun. 2018; 9(1):2983. PMC: 6065407. DOI: 10.1038/s41467-018-05190-9. View

20.

Marquardt J, Andersen J, Thorgeirsson S . Functional and genetic deconstruction of the cellular origin in liver cancer. Nat Rev Cancer. 2015; 15(11):653-67. DOI: 10.1038/nrc4017. View