Abstract 1471P
Background
Gastric cancer (GC) has poor prognosis and presents big heterogeneity and unknown mechanisms of drug resistance. Tumor organoids are a 3D in vitro culture platform from self-organizing tumor stem cells, which recapitulates the in vivo characteristics reflecting the heterogeneity of the original tumor. The establishment of gastric cancer organoids (GCO) represents a good strategy to evaluate tumor molecular features. GCO also permit testing drug resistance performing functional dynamical analyses, representing a relevant arm for precision medicine.
Methods
A prospective biobank of GCO derived from advanced GC patients, mostly from biopsies or palliative gastrectomy, was generated according to an in-house protocol from January 2019. Tissue samples were analyzed by a dedicated pathologist with immunohistochemistry for HER2, PD-L1, TILs and microsatellite status, tumor samples and GCO were also screened for EPCAM, CK7, CK20, CDX2 and MUC5A. The molecular profile was completed with next generation sequencing (NGS) analyses with an in-house panel (Illumina®) to match the original tumor and its GCO. To assess drug sensitivity, cell viability was analyzed through luminescent Cell Viability Assay.
Results
From February 2019, 25 GCO were established with a success rate of 68% (20 from gastroscopy, 3 from gastrectomy, 1 from ascites and 1 from pleural effusion). 64% of these tumors were intestinal, 24% diffuse and 12% mixed subtypes, according to Lauren classification. The organoids histopathological analysis matched with the original tumors. NGS analysis also showed a significant molecular concordance between the GCO and each original patient (R>0.90). The capability in reproducing GC heterogeneity was observed when GCO were generated from two different biopsies from the same patient. Copy number variation (CNV) analysis showed that only one of these lines was HER2+, being a mirror of the heterogenous expression of HER2 in the original tumor. Drug sensitivity assays were also performed to match the response observed in the GCO with each patient.
Conclusions
GCO could be a valuable tool for heterogeneity assessment as well as drug sensitivity for GC patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
This study was supported by grants from the Carlos III Health Institute (PI18/01508 to TF; PI15/02180 and PI18/01909 to AC). MC is supported by a pre-doctoral grant from the Spanish Cancer Association (AECC), Spain. FP is a recipient of an ESMO translational research grant. MFGB is a recipient of a Grisolia predoctoral grant (GRISOLIAP/2017/161) by the Conselleria de Educación, Investigación, Cultura y Deporte of Valencia. VG is supported by a Rio Hortega contract CM18/00241 from the Carlos III Health Institute. NT was supported by Rio Hortega contract CM15/00246 from the Carlos III Health Institute. DR was supported by Joan Rodes contract 16/00040 from the Carlos III Health Institute. TF is supported by 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): 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: Foundation Medicine; Research grant/Funding (institution): Genentech. All other authors have declared no conflicts of interest.