Nanobody E8 curbs abdominal cancer growth in lab and mouse tests

Patients with peritoneal metastases often develop ascites, a fluid that spreads through the body and carries proteins that promote cancer. For this disease, where the median survival is under nine months, the question was what exactly was inside that fluid. A team led by the National Cancer Center Singapore set out to answer it with one of what is believed to be the largest ascites datasets in the world.

The researchers used multiomic profiling, analyzing proteins and biological pathways across 397 samples from 21 primary cancer types. Two proteins, PAI-1 and S100A10, emerged as key drivers of tumor development in the ascites environment. A 2022 study by the same NCCS team had already shown that targeting ascites could inhibit tumor growth; the 2026 work went further by mapping the pathways and therapeutic vulnerabilities inside the fluid.

Rather than building a conventional monoclonal antibody, the team chose PAI-1 as its target and developed a nanobody, named E8. Nanobodies are a newer class of drugs, small in size, with low immunogenicity and reduced toxicity risk. In theory, these properties could make them better tolerated than many existing treatments, which matters for patients already in an advanced stage. E8 was tested in three settings: cell assays, mice, and human tumor tissue grown in patients' ascites. In all three, it suppressed tumor growth with minimal toxicity. These results come from the laboratory and from animal and tissue models; the article does not report human trials.

For patients, the practical gain would be a new type of treatment that acts on the fluid surrounding the tumor rather than on the tumor cells directly. The senior author, Associate Professor Johnny Ong of Singapore General Hospital, said the team now has "the possibility of offering a new class of treatments for peritoneal metastases". He added that the pathway "potentially has implications for any cancer that results in ascites", naming ovarian, gastrointestinal, liver, breast and lung cancers. The sources give no timeline for clinical testing, so for now E8 remains a candidate that must still prove itself in people. The step to watch is whether its effect on PAI-1 holds up beyond these models.