3D Organoids For Drug Screening and Personalized Medicine
- Technology Application
- Drug screening and developmentPersonalizationof therapeutic regimen
- Detailed Technology Description
- A novel platform for use of primary human normal and cancerouscells in screening new therapeutic candidates and to stratify patientsresponsive to specific drugs
- *Abstract
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Pancreatic cancer is one of the deadliestmalignancies. The late presentation of symptoms and high mortality highlights adesperate need for early detection methods and new treatment strategies. Morethan 95% of pancreatic cancers originate from the exocrine compartment of thepancreas, comprised of acinar and ductal cells. Among the exocrine tumors, 90%are pancreatic ductal adenocarcinoma (PDAC) which is the cause for most of themortality. Due to its rapid onset and progression, there is an unmet need torapidly identify the most effective therapeutic regimen for a patient.
UHN investigators have developed novelconditions (media and procedures) through which a 3D-culture of primary humanPDAC can be established within 14 days, maintained and propagated as organoidstructures. Initial analysis indicatesthat the tumor-organoids can be clonally derived and recreate thehistoarchitectural heterogeneity observed in the parent tumor, and can be usedas critical tools in the stratification of patients’ responsiveness to specifictherapeutic regimens, as well as offering a rapid way to identify novel cancertherapeutics. Using progenitor-organoids, a new clinically relevant phenotypeassociated with expression of mutant TP53 has been identified. Further, usingsuch tumor organoids has helped decipher patient-specific differences inresponsiveness to drugs, as well as the related underlying biology.
The potential use of this platform ishighlighted in these figures. Though pancreatic tumor organoids from patients 6and 17 seem to respond equally to the concentration of gemcitabine shown inFigure A, the organoids derived from the same two patients respond differentlyto a combination of gemcitabine and Drug A or Drug B, as shown in Figure B. Thedevelopment of this platform can dramatically expedite patient profiling in aclinical trial setting, and help replace the need for developing xenograftmodels of human cancers used in the drug development process, and further helpin identifying patients suitable for a specific treatment modality.
- *Publications
- Huang L. et al. Nat Med. 2015Nov;21(11):1364-71. doi: 10.1038/nm.3973. Epub 2015 Oct 26
- Country/Region
- USA
