- 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.
DOI: 10.1158/2159-8290.CD-24-0605
About Duke-NUS Medical School
Duke-NUS is Singapore’s flagship graduate-entry medical school, established in 2005 with a strategic, government-led partnership between two world-class institutions: Duke University School of Medicine and the National University of Singapore (NUS). Through an innovative curriculum, students at Duke-NUS are nurtured to become multi-faceted ‘Clinicians Plus’ poised to steer the healthcare and biomedical ecosystem in Singapore and beyond. A leader in ground-breaking research and translational innovation, Duke-NUS has gained international renown through its five Signature Research Programmes and ten Centres. The enduring impact of its discoveries is amplified by its successful Academic Medicine partnership with Singapore Health Services (SingHealth), Singapore’s largest healthcare group. This strategic alliance has led to the creation of 15 Academic Clinical Programmes, which harness multi-disciplinary research and education to transform medicine and improve lives.
For more information, please visit www.duke-nus.edu.sg
About the National University Cancer Institute, Singapore
The National University Cancer Institute, Singapore (NCIS) is an academic, national specialist centre for cancer under the National University Health System (NUHS), and is the only public cancer centre in Singapore that treats both paediatric and adult cancers in one facility.
As one of two national cancer centres in Singapore, NCIS (pronounced as “n-sis”) offers a broad spectrum of cancer care and management from screening, diagnosis and treatment to rehabilitation and survivorship, as well as palliative and long-term care. NCIS’ strength lies in the multi-disciplinary approach taken by our clinician scientists and clinician-investigators to develop a comprehensive and personalised plan for each cancer patient
NCIS provides the full suite of specialised oncology and haematology services at the NUH Medical Centre at Kent Ridge, Singapore, including those by the NCIS Chemotherapy Centre, NCIS Radiotherapy Centre and NCIS Cellular Therapy Centre.
NCIS also offers cancer services at other hospitals in Singapore:
- NCIS Cancer & Blood Clinic @ Ng Teng Fong General Hospital
- NCIS Radiotherapy Centre @ Tan Tock Seng Hospital
- NCIS Radiotherapy Clinic @ Khoo Teck Puat Hospital
To bring cancer care even closer to our patients, our NCIS on the Go programme delivers a range of cancer services at clinics within the community for their convenience.
For more information, please visit www.ncis.com.sg.
About National University of Singapore (NUS)
The National University of Singapore (NUS) is Singapore’s flagship university, which offers a global approach to education, research and entrepreneurship, with a focus on Asian perspectives and expertise. We have 16 colleges, faculties and schools across three campuses in Singapore, with more than 40,000 students from 100 countries enriching our vibrant and diverse campus community. We have also established more than 20 NUS Overseas Colleges entrepreneurial hubs around the world.
Our multidisciplinary and real-world approach to education, research and entrepreneurship enables us to work closely with industry, governments and academia to address crucial and complex issues relevant to Asia and the world. Researchers in our faculties, research centres of excellence, corporate labs and more than 30 university-level research institutes focus on themes that include energy; environmental and urban sustainability; treatment and prevention of diseases; active ageing; advanced materials; risk management and resilience of financial systems; Asian studies; and Smart Nation capabilities such as artificial intelligence, data science, operations research and cybersecurity.
For more information on NUS, please visit http://www.nus.edu.sg/
About the National Medical Research Council (NMRC)
The NMRC was established in 1994 to oversee research funding from the Ministry of Health and support the development and advancement of biomedical research in Singapore, particularly in the public healthcare clusters and medical schools. NMRC engages in research strategy and planning, provides funding to support competitive research grants and core research enablers, and is responsible for the development of clinician scientists through awards and fellowships. The council’s work is supported by the NMRC Office which is part of MOH Holdings Pte Ltd. Through its management of the various funding initiatives, NMRC promotes healthcare research in Singapore, for better health and economic outcomes.
