Bioengineered Tumor Model Aids Fight Against Abdominal Cancer

Researchers have developed a bioengineered hydrogel platform capable of preserving patient-derived tumor tissues for longer periods, a breakthrough that could enhance drug testing for peritoneal metastases – a challenging and often fatal form of abdominal cancer.

This new method significantly extends the life of tumor samples, offering a more reliable model for evaluating cancer treatments.

The research is published in Advanced Materials.

Advances in tumor preservation

The new hydrogel-based platform allows tumor tissues to remain alive and structurally intact for over 12 days. This is more than twice the duration achievable with current methods, which typically result in tissue degradation after only a few days in culture.

This advancement could prove pivotal for research into peritoneal metastases (PM), a condition in which cancer cells spread to the lining of the abdomen, most commonly originating from colorectal, ovarian or gastric cancers. The current lack of effective treatment options, combined with poor survival rates, underscores the urgent need for more accurate preclinical models.

“One of the key challenges in developing new therapies for PM has been the lack of realistic lab models that reflect the complexity of tumors in patients,” said team leader Eliza Fong, an assistant professor of biomedical engineering at the National University of Singapore.

"Our hydrogel overcomes this by maintaining not only the complex tumor composition but also its biological functions, including the immune and connective tissue components that play a critical role in how tumors respond to drugs," Fong explained.

Improved accuracy for drug testing

Conventional tumor models grown on inert surfaces often fail to replicate the complex environment of human tumors. These models can lose vital biological functions, including immune and connective tissue interactions that influence tumor responses to treatments. In contrast, the new hydrogel platform better mimics the body’s natural environment, supporting both the tissue’s biological activities and its structure, while preventing myosin II-mediated tissue contraction, which typically causes tissue breakdown.

The new model also features added ascites – a fluid that accumulates in the abdomens of patients with peritoneal metastases – to further enhance the model's authenticity and replication of conditions in the body. The researchers found that including ascites altered tumor response to chemotherapy, making them more drug-resistant. This finding also underscores the importance of including patient-specific factors in preclinical drug testing.

“Our goal was to develop a platform that better reflects the complexity of human tumors so we can evaluate drugs more reliably and tailor treatments to individual patients,” said associate professor Johnny Ong, co-leader of the study. 

Testing drug responses in a more realistic environment

Using their model, the researchers tested several standard chemotherapy drugs, including cisplatin and doxorubicin, as well as a novel experimental therapy targeting a protein found in ascites.

“The results from these tests showed that drug responses varied across patients, highlighting our model’s potential for personalising treatment," said Ong. 

Notably, the model retained key features of the original tumor environment. Single-cell RNA sequencing confirmed that major cell types - including immune cells, cancer-associated fibroblasts, and endothelial cells - were preserved in similar proportions to the original tumors. The hydrogel also maintained cell-to-cell communication patterns critical for understanding tumor behaviour and drug resistance.

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Crucially, the model was able to maintain key features of the original tumor environment. Using single-cell RNA sequencing, the team confirmed that major cells types (including immune cells, cancer-associated fibroblasts and endothelial cells) were preserved in similar proportions to the original tumor tissues. The hydrogel model was also able to maintain the cell-to-cell communication patterns critical for understanding tumor behavior and drug resistance.

This bioengineered hydrogel platform offers new hope for the development of personalized treatments for patients with peritoneal metastases. It could also serve as a valuable tool for drug development, helping to identify more effective therapies for a range of cancers with limited treatment options.

The researchers behind the new hydrogel platform believe that it could be a valuable tool for advancing drug development and precision oncology, enhancing the drug testing needed to develop therapies for patients with few current treatment options.

Reference: Wu KZ, Ding RH, Zhao Z, et al. Hydrogel‐mediated preservation of live tumor explants for drug development in peritoneal metastases. Adv Mater. 2025. doi: 10.1002/adma.202418647

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