Every Thursday, Laboratory Equipment features a Scientist of the Week, chosen from the science industry’s latest headlines. This week’s scientist is Samuel Denmeade from The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. He and a team found that a toxic weed called Thapsia garganica can fight cancer.
Q: What made you interested in studying Thapsia garganica to see if it could be used as a cancer drug?
A: Thapsia garganica is a weed that grows around the Mediterranean. It had been known for two thousand years that the plant was highly toxic. It was described by Pliny, Socrates and Galen. In Arabic it was known as the “death carrot” due to its ability to kill camels if they ate the plant. Up until the early 1900s, resins made from the plant were used medicinally as plasters to induce blistering to treat rheumatism and other diseases. Sometime in the 1970s our collaborator, Soeren Christensen in Copenhagen, discovered that the toxic principle in the plant was a chemical called thapsigargin.
Later we learned that thapsigargin had the ability to kill all cell types and, unlike chemotherapy, did not require the cells to be growing to induce death. Based on this we devised a strategy to target thapsigargin to cancer cells. Since the drug is highly toxic, we devised a prodrug strategy to inactivate the drug until it encounters specific proteases made by the cancer cells. We liken it to a molecular grenade that is inactive until the pin is pulled. In this case the cancer cells themselves pull the pin to bring about their own death.
Q: What are the future implications of your research and findings?
A: We are currently testing the prodrug called G202 in clinical trials in the US against a variety of cancer types with an initial focus on prostate cancer.
Q: What was the most surprising thing you found in your research?
A: The most surprising thing was that we could achieve a therapeutic index with this highly toxic compound and achieve excellent antitumor response against human tumors growing in mice.
Q: What is the take home message of your research and results?
A: This prodrug approach is a new platform for overcoming toxicity and resistance of cancer cells by delivering a highly toxic agent selectively to kill all of the cells within the tumor microenvironment neighborhood.
Q: What new technologies did you use in your lab during your research?
A: We mostly used old technologies, but we did have a heavy reliance on HPLC and ion-spray mass spectrometry to characterize the prodrugs in vitro and in vivo.
Q: What is next for you and your research?
A: We are continuing to optimize the prodrug approach and looking for ways to improve the efficacy of G202 against human tumors.