New combination drug controls tumour growth and metastasis in mice in lung and breast cancer hopefully will work in humans soon 21 Jul 2014 Researchers at UC Davis, University of Massachusetts and Harvard Medical School have created a combination drug that controls both tumour growth and metastasis. By combining a COX-2 inhibitor, similar to Celebrex, and an epoxide hydrolase (sEH) inhibitor, the drug controls angiogenesis (blood vessel formation), limiting a tumors ability to grow and spread. The study appeared in the journal Proceedings of the National Academy of Sciences. Weve been studying the effects of COX and sEH inhibitors, both by themselves and in combination, for several years, said senior author and UC Davis Distinguished Professor Bruce Hammock. We were surprised to find that the dual inhibitor was more active than higher doses of each compound, either individually or together. By combining the two molecules into one we got much greater potency against several diseases and completely unique effects in terms of blocking tumour growth and metastasis. Both COX and sEH enzymes control lipid signalling, which has long been associated with inflammation, cell migration, proliferation, hypertension and other processes. COX inhibitors block production of inflammatory and pain-inducing lipids, while sEH inhibitors preserve anti-hypertensive, anti-inflammatory and analgesic compounds. Separate COX and sEH inhibitors were previously found to work together in reducing inflammation and neuropathic pain. After testing individual COX-2 and sEH inhibitors, the team synthesised the drug (PTUTB), the first combined COX-2/sEH inhibitor. They then tested the dual inhibitor against human lung and breast tumours, both in vitro and in mice. They found that PTUTB blocked angiogenesis, inhibiting the proliferation of endothelial cells, which are critical to blood vessel formation. This in turn limited tumour growth and metastasis, reducing lung and breast tumour growth by 70 to 83 percent. In breast and lung cancers, the dual inhibitor blocked angiogenesis, which blocked the growth of solid tumours, said Hammock. This represents a new mechanism to control blood vessel and tumour growth. Robert Weiss, a co-author and professor of nephrology at UC Davis, added that the combination drug achieved the results with minimal side effects and no cardiovascular or gastrointestinal effects.
Posted on: Tue, 19 Aug 2014 21:50:47 +0000
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