Gastric Cancer Genomics and Beyond – Moving from Patient Samples to 3D Organoid Cultures for Integrative Genomics Analysis, Drug Sensitivity Assays, Cell Biological Studies and Animal Models

  • Project Details:
Project Code:T12-710/16-R
Project Title:Gastric Cancer Genomics and Beyond – Moving from Patient Samples to 3D Organoid Cultures for Integrative Genomics Analysis, Drug Sensitivity Assays, Cell Biological Studies and Animal Models
Project Coordinator:Professor Suet-yi LEUNG
Coordinating Institution:The University of Hong Kong
Participating Institution(s):Hong Kong Baptist University
The Chinese University of Hong Kong
  • Abstract
Gastric cancer (GC) is the third leading cause of cancer death worldwide, with high incidence in China and Hong Kong and highlighting the urgent need for new treatment methods. GC is a heterogeneous disease involving different combinations of mutations in cancer driving genes. Therefore, a one-size-fits-all approach to treatment is often not effective. Previously, we built a tissue bank of hundreds of patients, with clinical and pathological data, long-term patient outcome data and genomic data, including whole-genome/exome sequencing, gene expression profiling and methylation profiling. In this project, we generated a biobank of 3D organoids to compliment our existing tissue bank. Genomic studies were performed on the organoids and found to match the data collected from matched patient tissue, thereby providing a platform for individualised patient drug testing. Therefore, we used these organoids for large-scale drug screening, allowing us to correlate drug sensitivity with specific genomic perturbations. Moreover, we used the organoids to perform deep mechanistic studies of gastric cancer pathways, stem cell properties and drug resistance mechanisms, developing new mouse models for in vivo drug testing and novel methods for integrative analysis along the way. Overall, our results showed that organoids offer a drug screening platform that could guide patient treatment and clinical trials to accelerate anticancer drug development.
  • Research Impact
Professor LEUNG and the team have produced a gastric cancer organoid biobank with linked genomic data and paired original tumours, that represents a landmark bioresource for the cancer research community worldwide. Using this biobank, we continue to generate drug sensitivity data from large-scale drug screening, with subsequent linkage back to patient genomic data. As a result, we are able to utilise genomic technology to identify novel pathways, biomarkers, drug targets and driver genes of carcinogenesis, facilitating the future development of precision cancer therapies, identifying new therapeutic opportunities targeting combination driver alterations and potentially widening the usage of existing drugs.