Abstract 488P
Background
Organoids are 3D cultures derived from tissue or tumor specific stem cells that mimic the in vivo characteristics and cell heterogeneity. Cancer organoids enhance the current in vitro models allowing better understanding of cancer molecular features and make predictions of patient´s response to drugs. Among 30% of high-risk localized colorectal cancer (LCRC) patients do relapse despite optimal surgery. Our aim was to establish a biobank of organoids derived from LCRC patients to be added to the standard assessment as a first step to personalized treatment.
Methods
We generated a biobank of colon tumor organoids (CTOs) and normal colon organoids (CNOs) derived from patients with LCRC undergoing surgical resection. In some cases, two samples of the same tumor were collected and processed. The histopathological characteristics were evaluated and matched with the original tumor. Next Generation Sequencing (NGS) and Copy Number analysis (CNA) was performed to compare the genetic landscape of both the CTOs and frozen LCRC tissue. To assess drug sensitivity, cell viability was measured with the CellTiter-Glo® 3D Reagent 5 days after treatment.
Results
Localized organoids were established with a 78% success rate (patients n=40, CNOs=14, CTOs=31). From the established CTOs, 45% were located on the left colon, whereas 55% were on the right colon. Histopathological analysis confirmed the different epithelial cell subpopulations of the colon seen in vivo. NGS and CNA data exhibit a high concordance rate between the CTOs and the original tumor, reflecting the importance of 3D models as they recapitulate the original tumor mutational profile. Additionally, drug screening assays show different responses to 5-FU and Oxaliplatin among various CTOs.
Conclusions
We generated a patient-derived organoid biobank that recapitulate the mutational and CNA landscape of the primary tumor, suggesting our capability of reproducing LCRC patient’s tumor characteristics in vitro. Further studies are needed to determine their use as a tool for the identification of new molecular biomarkers of relapse and prediction of drug response.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
This work has been supported by the Ministerio de Economía y Competitividad. Instituto de Salud Carlos III with grants to Andrés Cervantes (PI15/02180 and PI18/01909) and Tania Fleitas (FIS PI 18/01508). MFGB is a recipient of a Grisolia predoctoral grant (GRISOLIAP/2017/161) by the CEICE of Valencia. FP is a recipient of an ESMO translational research grant. MC is a recipient of a predoctoral grant from the Spanish Cancer Association (AECC), Spain. VG is supported by a Rio Hortega contract CM18/00241 from the Carlos III Health Institute. TF is supported by a Joan Rodes contract 17/00026 from the Carlos III Health Institute.
Disclosure
A. Cervantes: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Merck Serono; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Roche; Advisory/Consultancy, Research grant/Funding (institution): Beigene; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Servier; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Takeda; Advisory/Consultancy, Research grant/Funding (institution): Astelas; Advisory/Consultancy: Pierre Fabre; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Fibrogen; Research grant/Funding (institution): Amcure; Research grant/Funding (institution): Sierra Oncology; Research grant/Funding (institution): Astra Zeneca; Research grant/Funding (institution): Medimmune; Research grant/Funding (institution): BMS; Research grant/Funding (institution): MSD; Speaker Bureau/Expert testimony: Angem; Speaker Bureau/Expert testimony: Foundation Medicine. All other authors have declared no conflicts of interest.