- Using cutting-edge spatial and genetic tools, Singapore scientists have uncovered two gastric cancer tumour subgroups, characterising their unique cellular states, immune responses and interactions with their surroundings.
- The team also identified separate evolutionary pathways of tumour cells, which can help predict the severity of disease.
- Their discoveries can potentially revolutionise stomach cancer therapy by unveiling new targets for precision diagnostics and treatment.
Singapore, 27 March 2025—A team of Singapore scientists has made a significant discovery in understanding stomach cancer, a disease that remains one of the deadliest cancers worldwide. By using advanced mapping technologies, they created a detailed “atlas” of stomach tumours, revealing hidden patterns in how cancer cells behave, evolve and interact with their environment. These insights could lead to more precise, targeted treatments that improve survival rates and reduce side effects.
Their study findings, published in Cancer Discovery, bring scientists closer to developing new treatments that can be customised according to the specific characteristics of a patient’s tumour, to more effectively target gastric cancer cells.
Using advanced experimental and computational methods, the team discovered distinct differences between cancer cells at the periphery and at the core of the tumour, providing valuable insights into how gastric cancer cells interact with their environment to grow and spread.
The research team from the Singapore Gastric Cancer Consortium, including doctors and scientists from Duke-NUS Medical School, the National University Cancer Institute, Singapore (NCIS) and the National University of Singapore Yong Loo Lin School of Medicine, also uncovered distinct evolutionary pathways of tumour cells, resulting in different immune responses driving tumour progression and treatment resistance.
Gastric cancer remains a formidable adversary, ranking as the fifth most common cancer and the third leading cause of cancer-related deaths worldwide, with more than one million new cases and close to 770,000 deaths each year. In Singapore, gastric cancer ranks among the top 10 causes of cancer-related deaths and claims about 300 lives[1] each year.
Combining state-of-the-art spatial technologies and genetic engineering tools
In this study, one of the most extensive of its kind, the team used recently available geospatial and genomic technologies to analyse 226 gastric cancer samples from 121 patients, from the National University Hospital and other institutes. Using a technology called spatial transcriptomics, they collated data from 2,000 microregions of the tumour samples, integrated with profiles of 150,000 single cells using single-cell RNA sequencing. Integrating these two approaches allowed the creation of a highly detailed map of gastric cancer tissues. The study spanned three years, from January 2022 to December 2024.
Professor Patrick Tan, a senior author of the study and Senior Vice-Dean for Research at Duke-NUS, said:
“The integration of spatial technologies and genetic engineering tools is like upgrading from an old roadmap to a high-tech GPS for cancer. Now, we can pinpoint exactly where cancer cells are in a tumour, how they behave and what makes them spread or stay put. This gives us a powerful tool to develop better treatments tailored to each patient, a tool with the potential to offer a valuable data resource for future exploration and discovery for scientists studying gastric cancer worldwide.”
Study findings: Identifying tumour subregions and evolutionary trajectories
The scientists identified two subgroups of cancer cells within the same tumour, with different surrounding types of immune cells and blood vessels that can contribute to tumour growth.
One subgroup comprised cells located at the tumour core. These cells were found to be marked by insufficient oxygen supply and were less likely to spread. The other subgroup, with cells located at the edge of the tumour, showed molecular features of highly invasive cells, which were more likely to spread.
By understanding such distinct interactions between tumour cells and their surrounding non-cancerous cells, researchers can identify critical pathways and genetic markers that influence tumour behaviour. For instance, the team discovered that non-cancerous cells bordering cancer cells were in a unique state driven by transforming growth factor-beta (TGF-β) signaling, a critical pathway involved in cell growth, differentiation, and immune response regulation. Targeting TGF-β signaling could inhibit the environment that promotes tumour growth and improve cancer therapy efficacy.
The team also uncovered separate evolutionary pathways that gastric cancers follow, each linked to specific prognostic outcomes. Taken collectively, these critical facets of tumour progression that the scientists identified, could expose gastric cancer’s Achilles’ heel, unveiling potential biomarkers for personalised therapies and offering differentiated treatment strategies to target various pathways.
Dr Raghav Sundar, one of the senior authors of the study and a senior consultant with the Department of Haematology-Oncology at NCIS, at the time of the research, explains:
“Our study breaks new ground in understanding the complex ecosystem of stomach cancer tissue with unprecedented spatial resolution. By employing advanced techniques, we've been able to meticulously map the interactions between various cell types within the tumor and its surrounding microenvironment of stomach cancer. This granular view allows us to see how cancer cells and their surrounding microenvironment influence each other and how this interaction drives tumor progression and resistance to treatments. These insights will be crucial in developing targeted therapies that can overcome the local barriers within the tumour microenvironment and effectively combat cancer.”
Armed with these new insights, the researchers are now working on identifying even more therapeutic targets for the treatment of gastric cancer, and testing them in pre-clinical models. Their goal is to develop smarter, more effective treatments that can be tailored to each patient’s tumour type–moving closer to truly personalised cancer care.
This research was supported by the National Research Foundation, Singapore (NRF) under the National Medical Research Council (NMRC) Open Fund-Large Collaborative Grant (MOH-000206) and administered by the Singapore Ministry of Health through the NMRC Office, MOH Holdings Pte Ltd; as well as the Singapore Gastric Cancer Consortium and Ministry of Education.