Oxford Scientists Break Blood-Brain Barrier to Allow
Cancer Drugs In
Source: ISIS Innovation
University of Oxford scientists have found a way of delivering drugs more effectively to treat life-threatening cancers that have spread to the brain, according to research published in the Journal of the National Cancer Institute Today (Wednesday)*.
The study, in mice and tissue samples, used a protein called TNF that can track down sites in the brain where cancer has spread by recognising a marker found only on tumour blood vessels.
The scientists from the Gray Institute for Radiation Oncology and Biology, found that TNF can home in on these sites and temporarily open the blood-brain barrier (BBB) allowing drugs to pass from the blood system into the tumour.
The BBB acts as a shield that prevents potentially dangerous particles such as bacteria entering the brain. But it’s this same shield that stops cancer drugs reaching tumours that have spread to the brain.
The TNF protein only broke down the BBB in the blood vessels that pass through the tumour, leaving the healthy parts of the brain undamaged by potentially toxic drugs.
The research shows that when TNF is injected into the bloodstream the breast cancer drug herceptin (trastuzumab) which is not normally able to cross the BBB, can reach cancer cells in the brain.
As well as preventing drugs reaching tumours in the brain, the BBB prevents the early diagnosis of the tumour’s spread to the brain as the dyes used to highlight the tumour cannot penetrate the BBB. This new approach will also allow diagnostic dyes to access the tumour and enable earlier diagnosis.
Study author Dr Nicola Sibson, who is funded by Cancer Research UK , said: “Treatments that work very well against the original site of the cancer lose their effectiveness when the cancer spreads to the brain – as these drugs are prevented from getting to the tumour because of the blood-brain-barrier.
“A number of attempts have been made to open up the BBB but they’ve all struggled because they’re either not specific enough to open the BBB only at the site of the tumour or not effective enough to allow the drug across to kill the cancer.”
The work is the subject of a patent application under management by Isis Innovation, the technology transfer company of the University of Oxford. Isis Innovation is inviting interest from prospective industry partners to support the translation of the work to the clinic.
Dr Louis Pymar, Isis Technology Transfer Manager in charge of the project, said: “This approach of selectively and transiently manipulating the permeability of the BBB to diagnostic and therapeutic agents, holds great promise for the early detection and treatment of brain tumours. In particular, breast cancers are known to preferentially spread to so-called ‘sanctuary’ sites in the brain, where otherwise effective treatments cannot follow; this work presents the opportunity to overcome this subversive advantage of malignant cells, and to restack the odds in favour of beating cancer.”
For further information about Cancer Research UK’s work or to find out how to support the charity, please call 0300 123 1022 or visit www.cancerresearchuk.org.
*Connell, J. J., et al Selective permeabilization of the blood-brain barrier at sites of metastasis Journal of the National Cancer Institute