Toxic Mediterranean "death carrot" could help treat cancer

In collaboration with the Press Association

A toxic chemical found in a Mediterranean plant is being developed into a potential new drug by an international team of researchers.

The plant Thapsia garganica – sometimes called the ‘death carrot’ – contains thapsigargin, an extremely toxic chemical.

It kills cells, including cancer cells, by blocking a protein called SERCA, which helps cells control their internal calcium levels. This makes thapsigargin toxic to both dividing and resting cells – unlike current cancer drugs, which target only cells that are rapidly dividing.

In theory this means that drugs based on thapsigargin could target slower-growing cancers as well as cancer ‘stem cells’ – the treatment-resistant cells that some researchers think fuel the disease.

In new research, published today in Science Translational Medicine, a team of US and Danish researchers have shown that an experimental drug based on thapsigargin is able to treat tumours in mice, and appears to be relatively non-toxic.

To create the experimental drug, the team  modified thapsigargin by linking it to a short protein-based molecule called a peptide, rendering it non-toxic.

The peptide is designed to only be removed by a second protein, known as PSMA, which is found in high concentrations on the surface of many different types of cancer.

This means that when the peptide-linked thiapsigargin – known as G202 - comes into contact with cancer cells that bear PSMA, the peptide is removed, and the thiapsigargin kills any cells in the immediate environment.

Henry Scowcroft, science information manager at Cancer Research UK, said the idea of a 'pro-drug', which uses an inert chemical which becomes activated once it gets near to a tumour, is not a new one, as other attempts have been made to create them in the past.

But he noted that trials of these drugs have often been unsuccessful because "either the drug doesn’t get sufficiently activated in the tumour, or, more usually, it is unstable and gets released into the bloodstream, causing unacceptable toxicity".

Recent advances in chemistry have started to address this problem, he added.

Commenting on the latest results, Mr Scowcroft added: "There are still many hurdles to be overcome. For example, we need to know how this experimental drug behaves in the bloodstream of people with cancer, rather than in laboratory models."

While it could eventually become a useful tool for doctors to combine with other treatments, he emphasised that the treatment still has to be proven to be safe and effective in large trials.

G202 is currently being tested on 28 US patients who have advanced cancer, to find out more about how toxic it is. Larger trials are planned if this proves successful.

Copyright Press Association 2012

References

  • Denmeade, S.R. et al. Engineering a Prostate-Specific Membrane Antigen–Activated Tumor Endothelial Cell Prodrug for Cancer Therapy. Sci Transl Med DOI: 10.1126/scitranslmed.3003886