Health World — 16 December 2011

Images show blood vessel growth in a retina (left image) and blood vessel growth blocked by the splicing switch (right image). Image courtesy of University of Bristol and UWE Bristol.

British scientists have discovered a new method of targeting cancer by manipulating a “master switch” responsible for cancer cell growth. Their study, published in the Cancer Cell journal, focused on how cancer cells produce their own blood vessels, allowing them to grow faster.

In order to gain nutrients, cancer cells produce proteins that make blood vessels grow, helping deliver oxygen and sugars to the tumor. These proteins, called vascular endothelial growth factor (VEGF), are targeted by anti-cancer drugs like Avastin. Producing the proteins requires slotting together different gene parts in a process called splicing.

Researchers from the University of West England Bristol and University of Bristol discovered that mutations in a specific cancer gene could control how splicing is balanced, allowing a master switch in the cell to be turned on. This master switch accelerates blood vessel growth, making tumors grow faster.

In experimental models, the researchers blocked the master switch using new drugs and discovered they were able to stop both blood vessel and cancer growth. This discovery could lead to new possibilities in cancer therapy and drug development.

“The research clearly demonstrates that it may be possible to block tumor growth by targeting and manipulating alternative splicing in patients,” said Dr. Micahel Ladomery, who spearheaded the work from UWE Bristol.

“This enables us to develop new classes of drugs that target blood vessel growth, in cancer and other diseases like blindness and kidney disease,” said Professor David Bates, who led the research team from the University of Bristol’s School of Physiology and Pharmacology.

The research involved patients with kidney cancer at Southmead Hospital in Bristol. The patients allowed their surgically removed tissues to be used in this research.

“We are really grateful to the patients who allowed their cells to be used in this research, as we hope it will eventually help the development of new drugs,” said Professor Moin Saleem, a Pediatric Nephrologist, whose lab helped to make the cells used.



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Neslie Tumulac

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