Hereditary Diffuse Gastric Cancer (HDGC) Research Update

The Hereditary Diffuse Gastric Cancer (HDGC) Research Fund supports the world-leading work of Professor Parry Guilford and the Cancer Genetics Laboratory at the University of Otago. Thanks to the generosity of donors, AUOA is able to channel 100% of contributions directly into this research — helping advance prevention strategies and improve outcomes for families affected by inherited stomach cancer.

This annual update highlights the progress made over the past year and demonstrates how philanthropic support continues to sustain discovery in a funding-intensive, high-risk field. Donor contributions act as essential “seed capital,” enabling researchers to pursue innovative scientific directions that traditional funding often cannot.

Otago’s Leadership in HDGC Research

The University of Otago has played a defining role in understanding and managing hereditary diffuse gastric cancer. In 1998, Professor Parry Guilford and colleagues discovered germline mutations in the CDH1 gene in Māori whānau with diffuse gastric cancer — a discovery that defined the HDGC syndrome and continues to shape global clinical practice today.

The Cancer Genetics Laboratory at Otago remains one of the most active and influential centres in the world for HDGC research. Its mission is to reduce the burden of inherited gastric cancer through genetic discovery, laboratory model development, and the pursuit of non-surgical prevention strategies for families carrying CDH1 mutations.

The team, led by Professor Guilford and including Dr Lyvianne Decourtye-Espiard and Dr Kieran Redpath, collaborates with scientists and clinicians across the globe. Their enduring partnership with Māori communities was recognised when Professor Guilford received the Prime Minister’s Science Prize (2023) for research that has transformed hereditary cancer care in New Zealand.

Research Highlights: 2024 – 2025

Decourtye-Espiard, L., Godwin, T. D., Guilford, P. J., et al. (2025). Hereditary Diffuse Gastric Cancer: The Evolution of a Cancer Syndrome. Journal of the Royal Society of New Zealand
This landmark review synthesises more than two decades of HDGC research, detailing advances in molecular understanding, pathology, and management strategies, and identifying an important “window of opportunity” for chemoprevention.

Redpath, K. (2024). Rational Design of Drug Combinations for Chemoprevention in Hereditary Diffuse Gastric Cancer.Doctoral Thesis, University of Otago.
This doctoral research explores synergistic drug combinations that selectively target CDH1-deficient gastric cells, refining Otago’s approach to identifying low-dose, safe regimens for potential clinical prevention.

Together, these works reaffirm Otago’s position as a global leader in HDGC research and demonstrate the team’s ongoing productivity and innovation.

Major New Initiative: 2025 – 2028

The next major phase of Otago’s work is the Health Research Council of New Zealand (HRC)-funded project:
Direct-to-Stomach Delivery of Drugs for the Chemoprevention of Inherited Stomach Cancer

Led by Professor Parry Guilford, with Dr Lyvianne Decourtye-Espiard as co-investigator, this NZ$1.2 million three-year project aims to develop a targeted drug-delivery platform that delivers compounds directly to the stomach lining — a crucial step toward creating a practical, non-surgical alternative to prophylactic gastrectomy for people with CDH1mutations.

This initiative builds directly on the foundational discoveries sustained by the HDGC Research Fund and moves the field closer to a safe and effective chemoprevention strategy for hereditary stomach cancer.

Laboratory Progress

Beyond the major publications, the Cancer Genetics Laboratory continues to make significant advances:

• Compound screening and prioritisation: Over 100,000 compounds screened to identify drugs that selectively kill CDH1-deficient cells while sparing healthy tissue, with several promising leads advancing to validation.
• Organoid and mouse models: New 3-D stomach organoids enable realistic study of early HDGC biology, while refined mouse models are being used to confirm therapeutic effects in vivo.
• Genetic discovery: Ongoing work with families meeting HDGC criteria but lacking CDH1 mutations aims to identify additional genetic contributors to inherited gastric cancer risk.
• Collaboration and leadership: Otago researchers continue to play a central role in updating global HDGC clinical guidelines and contributing to international research networks and shared databases.

The Role and Impact of Donor Support

Gifts to the HDGC Research Fund are applied in full to Otago’s Cancer Genetics Laboratory, providing flexible and immediate support for laboratory and translational research.

Philanthropic funding fills a crucial gap between major grant cycles — helping retain staff, sustain experiments, and pursue exploratory ideas that traditional funding cannot easily support. These contributions act as seed capital, empowering the research team to take the scientific risks required to achieve breakthroughs.

Donor support over the past year has directly enabled:

• Purchase of laboratory reagents and organoid culture media for new experiments.
• Screening and validation of novel drug combinations identified in the Redpath PhD work.
• Partial support for research staff conducting compound testing and data analysis.
• Continued collaboration and publication within international HDGC networks.

This flexible funding was essential to maintaining continuity and momentum within the programme — bridging vital gaps in the research pipeline.

Looking Ahead

With the 2025 HRC project now underway, the Otago team is well-positioned to translate laboratory findings into clinical applications that could transform patient care for HDGC families.

The continued generosity of donors worldwide ensures this momentum continues — keeping Otago’s HDGC programme at the forefront of hereditary cancer research and global collaboration.