Crocus “smart bomb” cancer cure? It’s a bit more complicated than that

The autumn crocus, Colchicum autumnale, source of colchicine

Today’s headlines bring us news of a ‘cancer chemotherapy breakthrough’ using a chemical derived from colchicine, found in crocuses.

According to the news coverage, this ‘new drug’ could ‘bring hope to millions’, ‘dramatically reduce side-effects’, and ‘kill tumours in one treatment’, because it acts as a ‘smart-bomb’ and only affects tumour cells. This sounds tremendously exciting, but the truth is that this is a long way from being a drug that could be used to treat patients.

So far, the chemical has only been tested in mice, and there are many more tests that need to be done before it makes it to clinical trials.

Let’s unpick the science behind the story, find out where it came from, and see where it sits in the broader context of cancer research.

Where did the story come from?

The headlines come from a talk due to be given today at the 2011 British Science Festival, which is this year in Bradford. The festival is a scientific outreach event organised by the British Science Association. The talk, by researchers from the Universityof Bradford, appears to be based on peer-reviewed work they published in July 2010.

The talk was press released by the University of Bradford press office in advance of the talk.

As far as we’re aware, the team haven’t published any new results since their 2010 paper.

What is colchicine?

Colchicine is found in crocuses and is used to treat gout, but is extremely poisonous. It has also been investigated as an anti-cancer agent.

The Bradford researchers, led by Professor Laurence Patterson, have been trying to tweak the colchicine molecule to make it less toxic, thus making it more suitable to investigate as an anti-cancer drug.

How could colchicine kill cancer cells?

Colchicine severely damages a cell’s internal scaffolding by blocking the action of a protein called tubulin. Because tubulin plays a vital role in helping cells divide in two, colchicine effectively stops cell division in its tracks – an important trait for any potential cancer drug.

Unfortunately, colchicine doesn’t just attack cancer cells – it will stop healthy cells from dividing too. As a result, colchicine is regarded as a poison, with similar effects on the body to arsenic.

One way round this problem, as Professor Patterson and his team have been investigating, would be to deliver colchicine directly to a tumour, and prevent it escaping around the rest of the body.

Targeting colchicine to cancer cells

In order to target colchicine directly to tumours, the researchers enlisted the help of a family of proteins called matrix metalloproteases, which are often produced in large amounts by many cancers.

MMPs are powerful enzymes that can dissolve the gelatinous gloop that surrounds our cells, known as the extracellular matrix. Cancer cells use it to clear a path for new blood vessels to grow towards them (during a process called angiogenesis), providing essential oxygen and nutrients.

To exploit this, the researchers used some clever chemistry to attach long molecular ‘tails’ to individual colchicine molecules. They found that this modified colchicine, called ICT2588, was less toxic to healthy cells, but if the ‘tail’ was hacked off by MMP enzymes then it was activated into the potent cell-killing form of the drug.

The idea is that in healthy tissues (which don’t have much MMP), the modified colchicine molecule is essentially harmless. But when it arrives in areas with lots of MMP – namely tumours – the tail is cut off and the drug is activated.

In turn, this activated colchicine would then poison anything in the vicinity, including any new-growing blood vessels. The overall effect would be to stop the cancer cells from growing, and starve the tumour of blood and oxygen.

That’s the theory. So far the researchers have tested their modified colchicine in mice carrying a variety of human tumours, including bowel, breast and lung cancers, and say they’ve cured about half the mice they’ve studied, in trials lasting around 2 months each.

But let’s be clear – this is a long way from curing human cancers.

How important is this research?

The researchers’ results so far are impressive, but they’re just one of several hundreds of similar intricate approaches taken to tackle cancer by researchers around the globe, which are generally referred to as ‘enzyme-prodrug therapy’, and involve activating a harmless form of a drug near or in a tumour.

For example, scientists we’ve funded have worked on more complex variations of the technique, where rather than relying on an inherent property of tumour cells (in this case, matrix metalloproteases), the cancer cells are artificially engineered to activate the prodrug – you can see press releases from our archives here, here, and here.

Overall it’s fair to say that this kind of approach is still at a relatively early stage, although the Bradford results are certainly impressive, and their beauty is in their relative simplicity.

And so to the headlines

The media reporting of this story has, in general, failed to emphasise the early nature of this work. Many questions remain to be answered.

For example, only half the mice in the studies were cured. Why weren’t the other half? How would this scale up to studies in people?

Several newspapers talked of “side effect-free drugs” or “dramatically reduced side effects”, but no effective drug is truly side effect-free – not even the new generation of targeted therapies that are currently emerging from clinical trials. The early results from the Bradford team tell us little about any potential human side effects of the modified drug, or even whether it would be safe to give to patients.

Another report initially got the name of the molecule wrong, calling it ‘coltrazine’, and claimed that it was already used to treat cancer (although this has since been corrected).

Finally, a common feature was the judicious use of the word ‘could’ throughout many of the articles, particularly in the headlines, allowing reporters to make claims that undoubtedly raised hopes of many people currently undergoing treatment for cancer.

In summary, this research is a small – although intriguing – step forward in the laboratory, but there are many hurdles still to clear for the Bradford team before their findings can be used to help the cancer patients of the future.

Cancer survival rates are rising, thanks to improvements in cancer detection and treatment brought by research. But while scientists need to keep the public informed and engaged with the progress they’re making, we all need to take care not to raise expectation and hope unduly.

Henry

• Image via Wikimedia Commons

Reference:

Atkinson, J., Falconer, R., Edwards, D., Pennington, C., Siller, C., Shnyder, S., Bibby, M., Patterson, L., Loadman, P., & Gill, J. (2010). Development of a Novel Tumor-Targeted Vascular Disrupting Agent Activated by Membrane-Type Matrix Metalloproteinases Cancer Research, 70 (17), 6902-6912 DOI: 10.1158/0008-5472.CAN-10-1440