New drug could hold the key to pancreatic cancer

The thunder god vine, or Lei Gong Teng, is a herb used in traditional Chinese medicine and believed by some to be of use in a variety of ailments from arthritis to kidney disease. The plant contains multiple active compounds, and one of the most promising of these is triptolide, previously shown to have potential as a drug for treating various cancers, including pancreatic cancers.

The 5-year survival rate for pancreatic cancer is only 5%, and in contrast to the advances made in treating other cancers in recent years, this rate has not improved significantly over the last 30 years. Attempts to develop new chemotherapeutic drugs have had little impact, at best adding only a few months or even weeks to life expectancy.

However despite its potent anti-cancer properties, which can be readily demonstrated in the lab, triptolide has proved to be of limited use as a drug. This is primarily because it does not dissolve well in water, one of the essential ‘drug-like properties’. Research published in Science Translational Medicine this month (http://stm.sciencemag.org/content/4/156/156ra139.full), however, presents a way around this problem. Researchers based at the University of Minnesota developed Minnelide, a modified synthetic version of triptolide. The modifications inhibit the activity of the drug, but they also make it water-soluble. This allows Minnelide to be administered and absorbed, and once it reaches its target, enzymes naturally occurring in the body’s tissues convert it back to its original form, allowing it to get to work.

Minnelide was tested extensively here, both in vitro with cultures of cancer cell lines, and in mouse models with xenografted human pancreatic tumours. In all tests it performed as well or better than gemcitabine, the current standard of care for chemotherapy in pancreatic cancer, and in fact worked in some scenarios where gemcitabine is completely ineffective.

Minnelide is as yet in the early stages of testing; the road from drug discovery to general therapeutic use is a long one, and the process may take several years. The first studies in human subjects are expected to start in December of this year. These will be Phase 1 trials, which usually involve testing in small groups of healthy volunteers, to establish safe dosages and measure side-effects. Only when the drug reaches the stage of randomised controlled trials in which its effectiveness is compared with existing treatments, will it be clear whether Minnelide can really live up to its promising beginnings.