Glioblastoma is one of the most aggressive forms of brain tumour and is extremely hard to treat, with only around 27 per cent of patients in England surviving for one year or more*.
One of the difficulties is that only a handful of conventional drugs are able to penetrate the blood-brain barrier – which controls the exchange of molecules between the brain and the blood circulating around the body. So when glioblastoma patients develop resistance to existing treatments, there are very few alternatives that doctors can try.
But now researchers from the University of Wolverhampton – funded by The Brain Tumour Charity (formerly Samantha Dickson Brain Tumour Trust) – have shown in lab studies how an anti-alcoholism drug called disulfiram, which can potentially cross the blood-brain barrier, might help sensitise cancer cells to existing chemotherapy treatments.
They found that the drug was effective at killing glioblastoma cells growing in the lab, particularly when combined with the chemotherapy drug gemcitabine, which is one of few chemotherapy drugs that can cross the blood-brain barrier. Problems with tumours developing resistance to gemcitabine have previously limited its use in treating this type of cancer.
And because disulfiram is already licensed for use in alcoholic patients, this paves the way for phase II clinical trials to begin in cancer patients as soon as possible.
Study leader Dr Weiguang Wang, from the University of Wolverhampton, said: “We’ve been studying the cancer-fighting properties of disulfiram for over a decade, so it’s very exciting to have reached a stage where clinical trials may be possible. These latest findings suggest that the drug may work by transporting copper into the cancer cells, generating destructive free-radicals that build up and kill the cell. Glioblastoma cells tend to have much higher levels of copper than normal tissues, meaning additional copper may tip them over the edge while sparing normal tissues.
“The idea of using copper to tackle cancer was first suggested by UK scientists in the 1920s, but this is the first time that scientists have found a way of successfully transporting excess copper into cancer cells and shown how this can be combined with conventional chemotherapy treatment to help kill glioblastoma cells. We’re now working on the best way to deliver dilsulfiram and hope to begin clinical trials in cancer patients as soon as funding can be secured.”
Sarah Lindsell, CEO of The Brain Tumour Charity, said: “The Brain Tumour Charity is proud to have funded this research and is pleased that it has had such a positive outcome that has the possibility of leading to clinical trials. We see first-hand the devastating effects that glioblastomas have on patients and their families and this research could be a foundation to improve treatment and extend life expectancy. It is only through funding much-needed research that we can offer real hope to people who are diagnosed with a glioblastoma in the future.”
Dr Julie Sharp, Cancer Research UK’s senior science information manager, said: “One of the big challenges in cancer treatment is how to successfully kill tumour cells without harming the surrounding tissues. Drugs like this one, which can both penetrate the blood brain barrier and increase the sensitivity of cancer cells to chemotherapy, could play an important role in overcoming the problem of resistance to help improve the outlook for people with brain tumours.”
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Peng Liu et al, Cytotoxic effect of disulfiram.copper on human glioblastoma cell lines and ALDH positive cancer-stem-like cells, British Journal of Cancer (2012), DOI: 10.1038/bjc.2012.442
Notes to editors
* National Brain Tumour Registry, NCIN CNS SSCRG work programme, Relative survival for Glioblastoma multiforme for residents of England, 2012.