The switch design only works for certain subsets of cancers, particularly non-small cell lung cancer cells with an EGFR gene mutation, where drugs that target the mutated proteins in the cancer cell are already on the market.
“We take a conservative approach to design and testing,” Pritchard said. “We will specifically look for faults in the switch and analyze what we find, much like when civil engineers analyze a fault in a building or bridge after the fact. Failures help us understand where our ideas about cancer treatment are incomplete and what we can do to correct them and increase our knowledge.
After initial testing on cancer cell lines, the researchers will test the double-switch gene drives on human organoids, provided by the University of Massachusetts Medical School, which are patient-derived cancer cells that mimic more closely from real tumors.
Co-investigator Shelly Peyton, Armstrong Professor of Professional Development at the University of Massachusetts Amherst and an expert in tissue engineering, will lead the design of microenvironments to determine how gene therapy works under different conditions. Peyton’s team will investigate how certain switches or settings fail, or why they work well in some environments but not others.
“The research here is trying to take the challenge of treating cancer and turn it around,” said Scott Leighow, a fifth-year doctoral student in biomedical engineering, who collected the preliminary data that was essential to winning the grant. “If we can do that, we’ll have a therapy that can handle resistant forms of cancer much better than what’s currently in our arsenal.”
If the study is successful, the researchers will test their treatments in animal models to show proof of concept, Leighow said. In the distant future, the technology has the potential to offer cell-based gene therapy that could help cancer patients who are not candidates for surgery.
The grant is part of a new consortium created by the NCI to promote collaborative synthetic biology approaches for cancer applications.