Key Points
- Researchers demonstrated that focused ultrasound plus an anti-cancer drug was effective in reducing tumor size in a model of prostate cancer.
- This preclinical study was a collaboration between Vanderbilt University Medical Center and Rice University.
Researchers at Vanderbilt University Medical Center and Rice University recently published results from a preclinical study suggesting that a combination of focused ultrasound with an anti-cancer drug was effective in reducing tumor size in a preclinical model of prostate cancer. The idea for the study emerged during a departmental social gathering where collaborating researchers Michael King and Charles Caskey discovered their shared interest in mechanosensitive channels and the potential impact of these channels on cancer therapy.
A small-molecule protein therapy called tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) has been shown to be effective at selectively causing tumor cell death while sparing healthy cells, but it has a short half-life. For TRAIL to be effective alone, patients would need multiple infusions a day. Recognizing the role of mechanosensitive ion channels in this process, the researchers theorized that combining TRAIL with low-intensity focused ultrasound could amplify its effects in prostate cancer models.
Certain types of mechanical movement can act as a trigger for cells to open Piezo1 ion channels. In this study, non-thermal, low-intensity focused ultrasound was evaluated to safely apply the pressure that activates these Piezo1 channels, causing calcium influx and making cancer cells more sensitive to TRAIL. The researchers tested the effects of TRAIL plus focused ultrasound on human cells in a culture and on mice with tumors made of human prostate cancer cells.
The study’s primary endpoint – to ensure that the adjacent healthy cells remained unharmed by the ultrasound – was achieved. Researchers also found that the combination therapy of 10 minutes of focused ultrasound exposure plus TRAIL was more effective in reducing the number of cancer cells and the size of tumors when compared with either therapy alone. There was also no thermal effect produced by the focused ultrasound that could assist cell death.
“We are extremely excited by the potential of this as a platform technology that can be used to target and mechanically sensitize tumors to TRAIL therapy in a wide range of organs, including the brain – which is difficult to access by other means,” commented Michael King, E.D. Butcher Professor of Bioengineering at Rice University, and senior author of the study.