In treating cancer patients, one problem researchers face is how to deliver as much of the therapeutics as possible directly to cancer cells, while sparing normal cells. Many are working on various delivery systems using nanotech, synthetic biology approaches, RNA interference, and more. Now, a group at Johns Hopkins University led by Samuel Denmeade is taking inspiration from nature, says New Scientist's Hannah Krakauer. In its study published in Science Translational Medicine, the group describes how it engineered an analogue of thapsigargin, a toxic substance found in the flowering Thapsia garganica plant — nicknamed the "death carrot" by the ancient Greeks because of its toxicity to sheep and cattle. "Thapsigargin typically works by passing through cell membranes and shutting down calcium pumps — essential for cell survival — on the inside of cells," Krakauer says. By adding an extra peptide chain to the toxin, Denmeade's team changed it enough to keep it from entering cells until is encounters an enzyme called PSMA, which is found the surface of prostate cancer cells. "PSMA cleaves the extra chain off the toxin, setting it free to do its devastating business," Krakauer adds.
Further, the toxin doesn't just kill cancer cells that are undergoing growth, but can also kill dormant tumor cells, and non-cancerous cells used by tumors to help them grow. "You can envision it as a grenade," Denmeade tells Krakauer. "One guy pulls the pin, but it kills all the guys standing around." As the researchers' animal trials were successful, they are now moving to phase I clinical trials in prostate cancer, Krakauer adds.