‘Tumor on a Chip’: Building a Better Model to Discover Superior Therapies
Shay Soker, PhD, has long believed the classic in vitro model of testing a drug candidate for anti-cancer activity – growing cancer cells in a Petri dish and testing possible agents against them – is problematic.
Primarily his concerns are that such a 2-dimensional model does not mimic the 3-dimensional nature of a tumor mass that generally is part of a tissue in the body.
Soker and his colleagues at the Wake Forest Institute for Regenerative Medicine (WFIRM) are building a bioengineered, 3-dimensional tumor model that mimics a real tumor.
The goal is that the 3-dimensional structure will not only mimic the architecture of the tumor, but will also include the stroma (the soft tissue around the tumor made up of fibroblast and endothelial cells), and the proteins that serve as communication lines between the tumor and healthy cells. Soker and his colleagues will then use a microfluidic system that profuses the bioengineered tumor to show how it is living and growing in real time.
In short, with their bioengineered “tumor on a chip,’’ Soker and his team are creating as close to a real human tumor as possible to open a new world of drug therapy investigation. Soker has shared his research at the National Institutes of Health, National Cancer Institute and National Science Foundation, and was published in March in the Annals of Biomedical Engineering.
The work Soker and his team are accomplishing is part of the broader mission of WFIRM in regenerative medicine, where research on creating tissue substitutes has gone on for almost a decades.
“By developing various methods of creating different tissues, each with multiple cell types, we realized that we had created a set of very powerful techniques that could be applied to create tissue models for drug development, for developmental biology studies and more,’’ Soker says.
“In drug development, companies have pretty much exhausted their chemical libraries. They have tested all of their molecules for known targets in regular subculture models,’’ Soker says. “What they need now is a new screening system to run the chemical bank on and see if they have in their arsenal of chemical molecules something that would interfere with tumor growth in a 3-dimensional tumor, like in our model.”
In addition, because the “tumor on a chip’’ model has the potential to show how a tumor metastasizes, industry partners can seek a therapeutic agent that might target not the tumor but the “communication lines’’ to block the cancer cells from traveling.
“If you want to win a war, what you want is to make sure the enemy units cannot communicate,’’ Soker says. “If you block communication, you’ve taken a great step toward defeating your enemy.’’
The team is working to show how tumor cells from actual patients can be incorporated into the “tumor on a chip” model and interact with the environment around the tumor, including the stromal cells, as well as monitoring how the tumor grows, invades and metastasizes.
Soker believes a complex “tumor on a chip” model will be completed within five years.
Partnerships with pharmaceutical companies will be important for two reasons, Soker says.
First, financial support from industry partners will enable expansion of the various collaborative teams involved in the project—including cell biologists, molecular biologists, cancer genomics, biomedical engineers and imaging specialists.
Second, scientists from pharmaceutical company partners could join the project, giving insight into creating models that would work best with their molecules for testing.
“Industry scientists can provide insights that we are not encountering,’’ Soker says. “We need to be educated on exactly what their needs are because if we are going to test some of their drugs, what they would like to see in a model is very important.’’
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