Hydrogels help predict how tissue characteristics affect cancer drug resistance

Courtesy of Monica C Nesselbush at The Harvard Crimson

Chemotherapy drugs don’t always work, thanks to resistance in cancer cells. Now, researchers from Harvard University’s Wyss Institute have found a way to analyze how the stiffness of the “extracellular matrix”--the material that surrounds cells--can affect drug efficacy in cancer treatment.

"To have success with chemotherapy and other drug therapies, we will likely need to screen their effectiveness against cells living in various environments, and not just assume that cells will always respond to a drug the same way that they would in conventional cell culture," said David Mooney, a professor of bioengineering at Harvard’s School of Engineering and Applied Sciences and a Wyss core faculty member, in a statement.

Using alginate hydrogels derived from a sugar found in brown seaweed, Mooney created a drug screening assay that can mimic the mechanical stiffness and other physical attributes of tumor tissue and healthy tissue, according to the statement.

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Along with Jae-Won Shin, a former Wyss postdoctoral fellow, Mooney built a 3-D microenvironment in which the matrix stiffness can be changed, allowing the treatment of cancer drugs in a variety of cellular environments. Researchers can then observe how the cancer cells respond to drugs in different types of tissue environments. They found that mechanics, or physical characteristics of the tissue, do affect cancer cells’ response: For many drugs, cancer cells were more resistant if the matrix was softer.

The platform could potentially be used to gauge cancer cells for a response to specific drugs, thus matching cancer patients to the most appropriate drug or drugs for their type of cancer and its location, according to the statement. The hydrogel could also be used to single out promising drugs early in development, as well as to personalize drug treatment to combat resistance in later stages of development.

And while the team initially applied the 3-D hydrogel to chemotherapy drugs, the possibilities are endless: "These engineered 3D hydrogels, which enable investigators to mimic the mechanical environment of cancers in different organs, also potentially offer a new approach to developing precision medicine therapies being that could be tailored to patient-specific tumor environments,” said Dr. Donald Ingber, the founding director of the Wyss Institute, in the statement.

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