A multi-institutional team of researchers led by chemists from The University of Texas at Arlington has published a paper in the Journal of the American Chemical Society that describes its discovery of a potent anti-cancer agent that works exceptionally well amid low oxygen concentrations.
The findings reported in the paper, “Anticancer Agent With Inexplicable Potency in Extreme Hypoxia: Characterizing a Light-Triggered Ruthenium Ubertoxin,” represent a major advancement in the battle to develop drugs that can destroy cancer cells in the most toxic tumor environments.
Sherri McFarland, professor of chemistry and biochemistry and the paper’s senior author, said her research team discovered the agent during its investigation to solve one of cancer therapy’s most pressing issues.
“Drug-resistant tumors often exhibit a phenomenon known as hypoxia, or low oxygen concentration, which promotes tumor growth and can render many treatments ineffective,” McFarland said. “The holy grail for researchers in our field is to make compounds that can kill cancer cells when oxygen levels are really low.”
The study introduces a chemical compound containing the transition metal ruthenium as a light-responsive, anti-cancer agent that is water-soluble, is inactive in the absence of a light trigger, is active in low-oxygen environments and exhibits extremely potent therapeutic characteristics using visible light. The anticancer effects on cancer cells reported in the paper are the largest to date for any compound class.
McFarland’s team specializes in photodynamic therapy, a cancer treatment that uses light to target and destroy tumor cells. Her lab develops and tests chemical compounds that, when exposed to light, produce a powerful oxygen reaction. The combination of transition metal compounds, light and oxygen generates highly selective cancer-fighting agents that do not affect surrounding healthy tissue.
One of her lab’s ruthenium-based photodrugs, TLD1433, is currently in a phase II clinical study for patients with recurring bladder cancer.
Houston Cole, first author and a fourth-year doctoral student under McFarland’s supervision, said seeing compounds transition from the lab to clinical human trials motivates his research.
“Day-to-day we are able to make the real-life connection from our explorations in the lab to drugs like TLD1433 that are making a difference in people’s lives,” Cole said. “We also draw inspiration from the scientific challenge to make effective drugs for hypoxic environments and understand how they work.”
Source: University of Texas at Arlington