Monday September 12 2011
The chemical comes from the autumn crocus flower
Many newspapers have reported today that a substance found in the autumn crocus, a flower native to Britain, has been turned into a “smart bomb” against cancer.
The newspapers reported that the targeted treatment ignores other types of tissue in the body, and circulates in the bloodstream before killing tumours by destroying the blood vessels that supply them. They say the treatment can be targeted at any solid tumour, regardless of cancer type.
Why is this in the news now?
The news reports have been prompted by a presentation made at this year’s British Science Festival being held in Bradford. The speaker was from the Institute of Cancer Therapeutics at the University of Bradford, where the research is taking place.
How does the treatment work?
The treatment aims to cut off the blood supply to solid tumours, essentially killing them by starving them of oxygen and nutrients.
The drug is based on a toxic substance called colchicine, a chemical derived from the autumn crocus, which is a flower that grows in Britain. The substance is normally toxic to tissues in the body, and so the researchers needed to find a way to target it to tumours and leave healthy tissue unharmed.
They did this by making an inactive form of the drug that is converted to its active form (“triggered”) by an enzyme (a type of protein) that solid tumours produce in order to grow and develop new blood vessels. This enzyme is one of a family of enzymes called the matrix metalloproteinases (MMPs).
The researchers anticipate that the inactive drug will circulate in the bloodstream, but when it comes into contact with the enzyme in the tumour, the toxic form of the drug will be released, killing off the tumour’s blood vessels and eventually the tumour itself. As the enzyme is only usually active at high levels in solid tumours, the drug will, in theory, not harm other healthy tissues.
What have the researchers done so far?
The press release for this presentation only contains a small amount of detail of the research and its results.
To date, the researchers report having tested the effectiveness of this therapy at treating tumours in mice. The treatment has reportedly been tested on five different types of cancer in the laboratory, including breast, colon, lung, sarcoma and prostate. These tests have reportedly been successful to varying degrees, with no adverse effects reported. The researchers report a greater than “70% cure rate after a single dose”.
Some of the work described at the festival may have been described in a related paper in the journal Cancer Research in 2010, entitled “Development of a novel tumour-targeted vascular disrupting agent activated by MT-MMPs”. This study focused on the effects of a derivative of colchicine, which the researchers called ICT2588, on one type of tumour in mice (fibrosarcoma), and did not appear to report all the results quoted in the press release.
Until the full results are published, including a full investigation of potential adverse effects, they should be seen as preliminary.
What did their published work find?
The published research used a derivative of colchicine, which the researchers called ICT2588. This drug is inactive until metabolised by a member of the MMP family called MT1-MMP.
The paper describes the level of production of the MMPs in different human cancer cells grown in the laboratory and on tumours grown from these human cancer cells in mice. They also looked at the effects of ICT2588 on the fibrosarcoma and breast cancer cells in the laboratory and in mice.
The researchers found that ICT2588 was being activated by the fibrosarcoma cells as they produced a high level of MT1-MMP, but not by the breast cancer cells that did not produce MT1-MMP.
Giving mice with fibrosarcoma tumours ICT2588 reduced the number of blood vessels feeding the tumours, and caused some of the tumour tissue to die, and tumour growth to slow down.
This study did not describe whether the mice had any adverse effects, although it did say that they did not lose weight after the treatment.
When will this treatment be available?
The researchers say that once the final pre-clinical trials are completed, the clinical trials are expected to start in the next 12 months.
This type of research is essential in the development and testing of new treatments for human diseases. Unfortunately, not all treatments that show promise in animals are as effective or safe in humans. We will need to await the results of the clinical trials to see whether this drug lives up to its promise. Such trials can take a few years before a drug is proven to be safe and effective enough for widespread use.
The researchers are optimistic about their findings but, as this is early stage research, also urge caution until more is known.
“We have to remain cautious until we can prove the same remarkable effects in clinical trials,” says Professor Patterson, “but ultimately, if all goes well, we would hope to see this drug used as part of a combination of therapies to treat and manage cancer.”