Turning cancer cells against themselves to overcome drug resistance

Penn StateJul 4 2024 But a team led by Penn State researchers has found a way to reprogram disease evolution and design tumors that are easier to treat.

This idea was born out of frustration. We're not doing a bad job of developing new therapeutics to treat cancer but how can we think about potential cures for more late-stage cancers?. Selection gene drives are a powerful new paradigm for evolution-guided anticancer therapy. I love the idea that we can use a tumor's inevitability of evolution against it."

"You're playing a game of Whac-A-Mole. You don't know which mole is going to pop up next, so you don't know what is going to be the best drug to treat the tumor. We're always on our back foot, unprepared," said Scott Leighow, a postdoctoral scholar in biomedical engineering and lead author of the study.

Related StoriesThe circuit has two genes, or switches. Switch one acts like a selection gene, allowing the researchers to turn drug resistance on and off, like a light switch. With switch one turned on, the genetically modified cells become temporarily resistant to a specific drug, in this case, to a non-small lung cancer drug.

The team first simulated the tumor cell populations and used mathematical models to test the concept. Next, they cloned each switch, packaging them separately into viral vectors and testing their functionality individually in human cancer cell lines. They then coupled the two switches together into a single circuit and tested it again. When the circuit proved to work in vitro, the team repeated the experiments in mice.

"The beauty is that we're able to target the cancer cells without knowing what they are, without waiting for them to grow out or resistance to develop because at that point it's too late," Leighow said.

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