Research team develops novel nanobody targeting tumor-fueling fluid to treat late-stage cancer of abdominal lining

by SingHealth

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

Now, a team of clinicians and scientists led by the National Cancer Center 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 tumor development.

Analyzing 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 tumor 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 tumor growth in laboratory, mouse and human tissue models with minimal toxicity.

The findings were published in the journal Molecular Cancer.

Associate Professor Johnny Ong, the study's senior author and head of the Department of Sarcoma, Peritoneal and Rare Tumors (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 tumor microenvironment via ascites, rather than the tumor cells directly.

"This pathway potentially has implications for any cancer that results in ascites."

Peritoneal metastases: Poor outcomes and limited treatment options

Peritoneal metastases originate from cancers of the primary organs in the abdomen, most frequently gastric (20%–25%), colorectal (20%–45%) and ovarian cancers (60%–75%), that have spread to the peritoneum, the lining of the abdominal cavity. Because they are often diagnosed only at stage IV, outcomes are poor and the disease is frequently managed with palliative intent.

Treatment options comprising surgery, regionalized chemotherapy and systemic chemotherapy remain limited in curative ability. This points to an urgent need to better understand the tumor 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 that contains proteins that actively promote cancer growth and that 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 tumor growth. The 2026 study went further to comprehensively characterize the biological pathways and potential therapeutic vulnerabilities within ascites.

Using multiomic profiling technologies, the team analyzed proteins and biological pathways across the 397-sample dataset spanning 21 different primary cancer types and found multiple key paracrine factors implicated in tumor development. Two proteins within this pathway, PAI-1 and S100A10, emerged as key drivers of tumor development within the ascites microenvironment.

Developing a novel nanobody to target the tumor 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 tumor tissue was grown in patients' ascites. Across all three, E8 effectively suppressed tumor 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 analyzing 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."

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."

So is also head and senior consultant, Division of General Surgery (Upper Gastrointestinal Surgery), Department of Surgery, National University Hospital, as well as head and 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 toward 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 program led by 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.

Publication details

Ying Liu et al., Identification of novel paracrine therapeutic targets in peritoneal metastases through integrative proteotranscriptomic analysis of ascites, Molecular Cancer (2026). DOI: 10.1186/s12943-026-02787-3

Journal information: Molecular Cancer

Key medical concepts

AscitesPlasminogen Activator Inhibitor 1

Clinical categories

Oncology Provided by SingHealth Who's behind this story?

Sadie Harley

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Andrew Zinin

Master's in physics with research experience. Long-time science news enthusiast. Plays key role in Science X's editorial success. Full profile →

Citation: Research team develops novel nanobody targeting tumor-fueling fluid to treat late-stage cancer of abdominal lining (2026, October 20) retrieved 20 October 2026 from https://medicalxpress.com/news/2026-10-team-nanobody-tumor-fueling-fluid.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.