Inside an incubator in Dr. Matthias Stephan's lab sits an unassuming assembly of tubing and syringes, pumping artificial saliva through a clear plastic column. The inner walls of the column are lined with mucus-secreting cells and near the bottom, a clump of cancer cells creates a blockage.
Simple as it sounds, this half-scale stand-in for the human esophagus is helping researchers test a bold new approach to treating an aggressive cancer that is on the rise.
Esophageal cancer is unforgiving. The disease is often not caught until it reaches advanced stages, when everyday activities like eating or drinking become painful, or even impossible. Existing treatment options like surgery are complex and risky. Chemotherapy and radiation can ease symptoms but seldom cure advanced disease and require expensive hospital stays.
Researchers from the Stephan Lab in the Translational Science and Therapeutics Division are working to develop a more effective and accessible treatment option for esophageal cancer: a powerful gene therapy delivered as a drinkable foam.
The team previously showed that a foam made of methylcellulose and xanthan gum, two commonly found food additives, can be used to safely and effectively deliver genetic instructions in the form of messenger RNA (mRNA) into cells. The mRNA molecules are relatively short-lived but can temporarily instruct cells to produce a specific protein, such as a cancer-killing protein derived from a bacterial toxin.
But even the most potent therapy is only useful if it can reach the right place. Tumors in the esophagus can be difficult to access, but the hope is that by incorporating this gene therapy into a drinkable foam, mRNA encoding cancer-killing proteins can be delivered directly to the tumor in a non-invasive manner.
To explore this possibility, the team first set out to understand how their foam formulation behaves compared to a liquid in their model esophagus, by adding a glowing dye to track their behavior in time-lapse videos.
As might be expected, the liquid rushed through the column, draining quickly and barely lingering at the site of the tumor in the model esophagus. The foam, however, quickly washed past the healthy upper portion of the model esophagus but slowed and accumulated once it reached the blockage created by the clump of cancer cells, settling exactly where the treatment would need to be delivered.
The team then tested whether this stable accumulation of the foam at the esophageal tumor actually translated into improved cancer-killing outcomes. They mixed mRNA encoding the cancer-killing protein into either a liquid or foam and measured how effectively each approach triggered cancer cell death.
The results were striking. Not only was the foam 110 times more effective at killing cancer cells in the model esophagus than the same therapy delivered in liquid form, but it also seemed to work in synergy with radiation therapy. The gene therapy foam made radiation over 30 times more effective at eliminating cancer cells compared to radiation therapy alone, suggesting that the two treatments could work together in a powerful combination to treat esophageal cancer.
This research is in its early stages, and much work remains before this approach can be tested in patients. But the underlying concept is a promising and significant departure from how esophageal cancer is treated today.
“Gene therapy foam could be a game-changer for esophageal cancer patients,” says Dr. Stephan, “as it could provide them with a potentially curative treatment option that can be administered orally in minutes by their family doctor.”
The implications of this work may extend beyond esophageal cancer. The team believes the same foam platform could be adapted for other cancers that constrict internal passages, such as advanced rectal cancer, which remains notoriously difficult to treat. The promise is not just a new therapy, but a new way of thinking about how gene therapy can be made simpler, more affordable, and more accessible to patients.
Fred Hutch/University of Washington/Seattle Children’s Cancer Consortium Member Dr. Matthias Stephan contributed to this research.
The spotlighted research was funded by the Fred Hutch Immunotherapy Initiative, with funds provided by the Bezos family foundation.
Stephan SB, Cummings CL, Fitzgerald K, and Stephan MT. 2026. Drinkable gene therapy foam for the treatment of constrictive esophageal carcinoma. Gene Therapy. DOI: 10.1038/s41434-026-00592-7
Science Spotlight writer Thamiya Vasanthakumar is a postdoctoral research fellow in the Campbell Lab at Fred Hutch. As a structural biologist, she uses cryogenic electron microscopy (cryoEM) to visualize the molecular structures of receptors found on the surface of immune cells.
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