Patient-derived organoids model treatment response of metastatic gastrointestinal cancers

Abstract

Patient-derived organoids (PDOs) have recently emerged as robust preclinical models; however, their potential to predict clinical outcomes in patients has remained unclear. We report on a living biobank of PDOs from metastatic, heavily pretreated colorectal and gastroesophageal cancer patients recruited in phase 1/2 clinical trials. Phenotypic and genotypic profiling of PDOs showed a high degree of similarity to the original patient tumors. Molecular profiling of tumor organoids was matched to drug-screening results, suggesting that PDOs could complement existing approaches in defining cancer vulnerabilities and improving treatment responses. We compared responses to anticancer agents ex vivo in organoids and PDO-based orthotopic mouse tumor xenograft models with the responses of the patients in clinical trials. Our data suggest that PDOs can recapitulate patient responses in the clinic and could be implemented in personalized medicine programs.

A fast and simple fluorometric method to detect cell death in 3D intestinal organoids

“…The method is cheap, reliable, and does not require commercially available kits, or complicated and time-consuming high content imaging analysis [21,25]. Thus, it is applicable for analysis of treatment-specific organoid death without the need to invest in expensive equipment or bioinformatics.…”

“…In this regard, patient-derived tumor organoid (PDOs) from pancreatic, prostate and gastrointestinal cancer are being used to model drug responses of patient-specific tumors in comparison to normal parental tissue [17–22]. This is of particular interest, as in gastrointestinal cancer it has been demonstrated that the parental and the PDO mutational spectra overlap up to 96%, on top of histological similarities [21]. …”

“…Thus, by closely resembling the primary tumor in vivo drug testing in PDOs represents a further step towards personalized medicine [21]. Moreover, organoid-like 3D primary cell culture models are being effectively used to screen a large number of emerging oncology compounds for their cytostatic and cell death-promoting activity [23].…”

Engineering Precision Medicine

“…c) The optimization of the microfabricated grooves for aligning cardiac cells. [171] Biopsies from liver cancer, [172] gastrointestinal cancer, [173] head and neck squamous cell carcinoma, [174] ductal pancreatic cancer, [175] and prostate cancer [176] have been used to create organoids in vitro. [150] Copyright 2018, Springer Nature.…”

Taking it to the gut

“…They can also examine drug response in the tissues and look for molecular profiles that indicate how well a patient may respond to treatment [4] In fact, researchers just reported in Science that organoids derived from patients with gastrointestinal tumors could accurately predict patient responses to chemotherapies. [5]. …”