Scientists from the Cancer Research UK-MRC Gray Institute for Radiation Oncology & Biology at the University of Oxford showed that treating mice with certain drugs improved the stability of blood vessels in the tumours. Normally, these blood vessels are badly developed, weak and twisted and as a result cancer cells have lower oxygen levels than normal cells.
But by improving the blood vessels the scientists increased the oxygen concentration inside the tumour – an effect that boosts tumours’ sensitivity to radiotherapy.
A better, more stable blood supply in the tumour also enables better delivery of chemotherapy drugs to the cancers.
Professor Gillies McKenna, director of the Institute, said: “We are very excited to have uncovered this brand new approach to cancer treatment – where the drugs prime the cancer cells for radiotherapy.
“It’s a counterintuitive technique because you might expect that by increasing an oxygen supply to tumour cells you would help them grow – but actually by oxygenating the cell with a better blood supply we enable radiotherapy and chemotherapy to do a better job of killing them.”
The scientists tested the effects of four drugs* which are in clinical use or under development for cancer therapy. The drugs block a cell signalling pathway which is commonly activated in cancer cells. The drugs were given to the mice at doses which did not alter tumour growth but the effects of the drugs acted to increase the blood supply to the tumours.
Professor McKenna added: “Previous work by our group had shown that treatment with some of these types of drugs could improve radiotherapy, but it was not understood how. Now with the new understanding, strategies could be developed to use these drugs to ‘soften up’ tumour cells before treating them with radiotherapy.”
Dr Lesley Walker, Cancer Research UK’s director of cancer information, said: “For a long time scientists have been looking for ways to boost the oxygen supply to tumours to improve response to treatment and make radiotherapy even more effective. “We still need to do more work on this technique but boosting the effects of radiotherapy and chemotherapy are very exciting developments that hold real potential for use in patients.”
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Qayum, N., Muschel, R., Im, J., Balathasan, L., Koch, C., Patel, S., McKenna, W., & Bernhard, E. (2009). Tumor Vascular Changes Mediated by Inhibition of Oncogenic Signaling Cancer Research, 69 (15), 6347-6354 DOI: 10.1158/0008-5472.CAN-09-0657
*The inhibitors blocked the epidermal growth factor receptor-RAS-phosphatidylinositol 3-kinase-AKT pathway (EGFR-RAS-PI3K-AKT). The drugs tested were: Iressa, Nelfinavir, PI-103, L778,123.