Johns Hopkins scientists have developed a novel anti-cancer drug made from a toxic weed-like Mediterranean plant that destroys cancer tumors and their direct blood supplies like a "molecular grenade," while sparing healthy tissues.
In laboratory studies of mice, the drug – called G202 – reduced the size of human prostate tumors by an average of 50 percent within 30 days. It also outperformed the chemotherapy drug docetaxel, reducing seven of nine human prostate tumors in mice by more than 50 percent in 21 days. Docetaxel reduced one of eight human prostate tumors in the same time period.
Researchers, who reported their findings in the journal Science Translational Medicine, said G202 also was also shown to be effective in laboratory model tests involving human breast cancer, kidney cancer and bladder cancer.
The researchers, with Johns Hopkins Kimmel Cancer Center, are now proceeding with clinical trials to test the safety and effectiveness of the drug involving people with advanced cancer, as well as prostate and liver cancer.
G202 is derived from a weed called "thapsia garganica" that grows in the Mediterranean region. The plant makes a substance, dubbed thapsigargin, known to be toxic since the time of ancient Greece. In Arab caravans, the weed was called the "death carrot" because it would kill camels if they ate it.
Researchers said they designed the drug from the toxin to travel safely – undetected by normal cells – through the bloodstream until activated by specific cancer proteins to target only tumor cells.
"Our goal was to try to re-engineer this very toxic natural plant product into a drug we might use to treat human cancer," said lead researcher Dr. Samuel Denmeade, a Johns Hopkins professor of oncology, urology, pharmacology and molecular sciences. "We achieved this by creating a format that requires modification by cells to release the active drug."
By re-engineering the toxin, Denmeade said researchers created a drug he likened to a hand grenade with an intact pin. The drug can be injected and can travel through the bloodstream until it finds cancer cells which trigger G202 to "pull the pin" and release agents that destroy tumors and the blood vessels that feed them.
"The exciting thing is that the cancer itself is activating its own demise," said co-researcher John Isaacs.