SG Research Team Develops Novel Nanobody Targeting Tumour-Fuelling Fluid to Treat Late-Stage Cancer of the Abdominal Lining

• Peritoneal metastases, a late-stage cancer that has spread from the abdominal organs to the abdominal lining, is fuelled by surrounding fluid called ascites, but its molecular makeup has never been comprehensively mapped until now. 
• A study led by the National Cancer Centre Singapore (NCCS) analysed one of the largest ascites datasets in the world; 397 samples across 21 cancer types and identified two proteins, PAI-1 and S100A10, as key drivers of tumour growth. 
• Building on this, the team developed a novel nanobody, E8, targeting the protein PAI-1, and demonstrated the nanobody can suppress tumour growth in lab, animal, and human tissue models with minimal toxicity. 
• A new biologics programme, the Melyorax Initiative, will advance E8 and other novel treatment strategies towards clinical trials for patients who currently have limited treatment options.

Singapore, 19 October 2026 – Peritoneal metastases, a late-stage cancer that has spread to the lining of the abdominal cavity, carries a median survival of under nine months and currently has few effective treatments. A build-up of fluid in the abdomen known as ascites is known to actively fuel tumour growth, but the molecular contents of this fluid and mechanisms by which it drives cancer growth, have remained poorly understood.

Now, a team of clinicians and scientists led by the National Cancer Centre Singapore (NCCS), in collaboration with A*STAR Institute of Molecular and Cell Biology (A*STAR IMCB), Singapore General Hospital (SGH) and the Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine), has conducted a large-scale analysis of ascites to map its protein landscape and uncover the biological pathways driving tumour development. Analysing what is believed to be one of the world's largest ascites datasets, the team identified two proteins, PAI-1 and S100A10, as key drivers of tumour growth in the ascites microenvironment. Building on this discovery, the team then developed a novel nanobody called E8 that targets PAI-1 and demonstrated that it can suppress tumour growth in laboratory, mouse, and human tissue models with minimal toxicity. The findings were published in the high-impact journal, Molecular Cancer, in September 2026.

Associate Professor Johnny Ong, the study's senior author and Head of the Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology at SGH and NCCS said, "With our team’s discovery of these proteins that are the key drivers of cancer growth and our subsequent development of E8, we now have the possibility of offering a new class of treatments for peritoneal metastases that targets the tumour microenvironment via ascites, rather than the tumour cells directly. This pathway potentially has implications for any cancer that results in ascites."

Peritoneal metastases: Poor outcomes and limited treatment options

Peritoneal metastases originates from cancers of the primary organs in the abdomen, most frequently gastric (20-25%), colorectal (20-45%) and ovarian cancers (60-75%),¹ that have spread to peritoneum, the lining of the abdominal cavity.² Because it is often diagnosed only at Stage IV, outcomes are poor and the disease is frequently managed with palliative intent. Treatment options comprising surgery, regionalised chemotherapy, and systemic chemotherapy remain limited in curative ability. This points to an urgent need to better understand the tumour biology of peritoneal metastases to develop new therapeutic strategies that can meaningfully improve patient outcomes.

Mapping the ascites microenvironment

Patients with peritoneal metastases frequently develop ascites, a fluid which contains proteins that actively promote cancer growth and spreads throughout the body. Other cancers associated with ascites include ovarian, gastrointestinal, liver, breast, and lung cancers, implying that insights from this study could be applied to cancers other than peritoneal metastases.

The NCCS team had investigated the role of ascites in peritoneal metastases in an earlier 2022 study, establishing that it was possible to target ascites to inhibit tumour growth. The 2026 study went further to comprehensively characterise the biological pathways and potential therapeutic vulnerabilities within ascites. Using multiomic profiling technologies, the team analysed proteins and biological pathways across the 397-sample dataset spanning 21 different primary cancer types and found multiple key paracrine factors implicated in tumour development. Two proteins within this pathway, PAI-1 and S100A10, emerged as key drivers of tumour development within the ascites microenvironment.

Developing a novel nanobody to target the tumour microenvironment

The team selected PAI-1 as a therapeutic target as it has clinical and prognostic relevance in cancer progression. Rather than developing a conventional monoclonal antibody, typically used in conventional immunotherapy, the team focused on developing a nanobody. Nanobodies are a newer class of drugs that are small in size and have low immunogenicity as well as reduced toxicity risk. In theory, these properties would make nanobodies better tolerated than many existing treatments, which is an important consideration for patients already in an advanced stage of disease. The nanobody E8 demonstrated therapeutic efficacy and safety across multiple model systems: in vitro cell assays, in vivo mouse models, and ex vivo human tissue explant models in which tumour tissue was grown in patients' ascites. Across all three, E8 effectively suppressed tumour growth with minimal toxicity.

Dr Joe Yeong, co-author of the study and Principal Investigator at A*STAR IMCB said, “The success of this study reflects the value of close collaboration between clinicians and research scientists. By analysing one of the world's largest ascites datasets, we uncovered critical mechanisms driving peritoneal metastases and translated these discoveries into E8, a promising nanobody therapeutic candidate with the potential to improve outcomes for patients with limited treatment options.” Dr Yeong also holds the position of Director of Immunopathology at SingHealth Duke-NUS, and Principal Investigator with the Department of Anatomical Pathology, SGH.

Professor Jimmy So, Department of Surgery, NUS Medicine, said, “This discovery is particularly encouraging because of its potential to pave the way for an effective therapy for peritoneal metastasis, a common and often deadly complication of many abdominal cancers. We hope this research can ultimately translate into better treatment options and renewed hope for patients facing this difficult condition.” Professor So is also Head and Senior Consultant, Division of General Surgery (Upper Gastrointestinal Surgery), Department of Surgery, National University Hospital, as well as Head & Senior Consultant, Division of Surgical Oncology, National University Cancer Institute, Singapore.

Taking the nanobody to the clinic: The Melyorax Initiative

The team is now working to advance E8 towards clinical-grade development and a first-in-human clinical trial. In parallel, they are developing a companion biomarker test to identify patients with elevated PAI-1 levels who are most likely to benefit from treatment with E8. These efforts come under a newly established biologics research programme led by Assoc Prof Ong, called the Melyorax Initiative, a name derived from the Latin melior, meaning "to make better." The Melyorax Initiative’s mission is to develop novel treatment strategies for patients with limited options, with E8 as its lead asset.

¹Foster JM, Zhang C, Rehman S, Sharma P, Alexander HR. The contemporary management of peritoneal metastasis: A journey from the cold past of treatment futility to a warm present and a bright future. CA A Cancer J Clinicians. 2023;73:49–71. https://doi.org/10.3322/caac.21749

²Menon G, Santillan VR. Peritoneal Surface Malignancies. [Updated 2025 Aug 9] In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 [cited 2026 Sept 15]. https://www.ncbi.nih.gov/books/NBK541114. Accessed 15 Sept 2026

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This study is supported by the SingHealth Duke-NUS Academic Medicine (AM) & National Health Innovation Centre (NHIC) MedTech Grant (AM-NHIC-JMT041/2022) and by the National Research Foundation, Singapore (NRF) under the NMRC Open Fund – Large Collaborative Grant (MOH-001793, MOH-001573) administered by the Singapore Ministry of Health through the NMRC Office, MOH Holdings Pte Ltd.

Study citation: Liu, Y., Chong, C.Y.L., Wang, Y. et al. Identification of novel paracrine therapeutic targets in peritoneal metastases through integrative proteotranscriptomic analysis of ascites. Mol Cancer 25, 225 (2026). https://doi.org/10.1186/s12943-026-02787-3

For media enquiries, please contact:

Dharshini Subbiah
National Cancer Centre Singapore
Corporate Communications
Email : dharshini.subbiah@nccs.com.sg

About the National Cancer Centre Singapore

The National Cancer Centre Singapore (NCCS) is a leading national and regional tertiary cancer centre dedicated to advancing cancer care, research and education. With a comprehensive suite of specialties and services, NCCS treats all cancers and offers personalised and multidisciplinary care to ensure that patients receive holistic, compassionate care and support. Advanced and innovative treatments such as proton therapy at the Goh Cheng Liang Proton Therapy Centre, immunotherapy, and cell therapy are available at NCCS to give patients the best treatment outcomes.

Ranked among the top cancer centres in Asia, NCCS is globally recognised for its research expertise, with clinicians and scientists collaborating with local and international partners to conduct cutting-edge clinical and translational research that makes a real impact and offers hope of a cancer-free tomorrow. As an academic healthcare institution, NCCS is committed to nurturing future generations by delivering specialised training to local and overseas oncology healthcare professionals. For more information, please visit www.nccs.com.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.

About the National Research Foundation (NRF)

The National Research Foundation, Singapore (NRF), set up on 1 January 2006, is a department within the Prime Minister’s Office. The NRF sets the national direction for research and development (R&D) by developing policies, plans and strategies for research, innovation and enterprise. It also funds strategic initiatives and builds up R&D capabilities by nurturing research talent. Learn more about the NRF at www.nrf.gov.sg.