Fighting cancer: Innovative strategy targets drug resistance in tumors

November 11, 2024November 7, 2024

A Clemson University professor said the cancer research he and his team are conducting could be a step toward treating tumors with drug combinations, turning them from potential death sentences into chronic but treatable diseases.

Marc Birtwistle, a professor of chemical and biomolecular engineering, said the team is working on a new strategy to fight cancer that focuses on how cells switching from one state to another complicates efforts to fight the disease.

The research will focus on glioblastoma, an incurable brain tumor, but the problem the project focuses on is common across all human cancers, he said. Developing new treatments resulting from research would take several years, Birtwistle said.

The five-year project is funded by $2.6 million from the National Cancer Institute and the Physical Sciences in Oncology Network. Project partners include Professor James M. Gallo, Assistant Professor Yeh-Hsing Lao and Associate Professor Ashlee Ford Versypt, all of the University at Buffalo; and Assistant Professor Sai Ma of the Icahn School of Medicine at Mount Sinai.

One of the difficulties in cancer treatment today is that drugs often become less effective over time and new treatments are required. Previous research has shown that the way cells switch between different states plays a key role in drug resistance.

In the new project, researchers want to develop therapies that keep cancer cells in a drug-sensitive state, making it more difficult for them to become resistant.

Ultimately, it could result in drug combinations that contain the different states that tumor cells could adopt, Birtwistle said. The approach could work similarly to drug combinations in treating HIV, although cancer is more complex, he said.

Researchers call their proposed treatment Cell State-Network-Directed Therapy.

“You would have to take these medications every day, but otherwise you could live a healthy, great life,” Birtwistle said.

In a laboratory, researchers will grow glioblastoma cells derived from three different patients. Researchers will then use advanced tools, including cutting-edge tumor-on-chip systems, to study how cells change state.

First, they will study cells without drugs to better understand how cell state networks behave. Then researchers will perform the same experiments in the presence of dozens of different drugs that cross the blood-brain barrier and are likely active at cell state network transitions, looking for drugs that kill cells or stop them from growing.

Researchers will feed this information into computer models to predict how cells will respond to combinations of different drugs, and then test those drugs individually and in combinations.

They will test the most promising drug combinations in 3D models that replicate real tumors. Researchers will analyze the results, refine their approach and work to develop treatments that prevent cancer cells from becoming resistant.

The work is intended to help narrow down the number of possible drug combinations for treating cancer. The Food and Drug Administration has approved about 350 different cancer drugs, and that doesn’t include the drugs sometimes used to fight cancer, Birtwistle said.

In total, there are about 7 million different drug combinations, he said. There are too many to conduct clinical trials on all of them in a reasonable amount of time, and why Birtwistle’s expertise in computer modeling will be crucial. The computational models will help the team narrow down which drug combinations appear most promising.

David Bruce, chair of the Department of Chemical and Biomolecular Engineering, congratulated Birtwistle and his team on securing funding for the research.

“Marc’s hard work and innovative approach make him the ideal leader for this research,” said Bruce. “This grant not only enables his team to improve outcomes for cancer patients, but also strengthens the department’s reputation for conducting impactful, cutting-edge research.”