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Why targeted cancer therapies sometimes fail

Posted on Mar 17 2014 | IANS

London, March 17 : Researchers have found clues as to why the recent trend of narrowly-targeted cancer therapies have not worked for some patients.

Take for instance, angiosarcoma, a rare cancer of blood vessels, with just 100 people diagnosed with it in Britain each year. The survival rates are poorer than many other cancer types.

Scientists have previously developed drugs against angiosarcoma that target specific cellular pathways involved in the formation of blood vessels. However, these drugs have had little or no success.

A team of researchers have now found that 40 percent of angiosarcomas carry mutations in genes that control blood vessel growth, including two novel cancer genes, PTPRB and PLCG1.

The findings of the study have appeared in the advance online publication of the journal 'Nature Genetics'.

"Because this cancer doesn't respond well to traditional chemotherapy and radiotherapy, it makes sense to develop drugs that target pathways that control blood vessel formation," Dr Peter Campbell of Wellcome Trust Sanger Institute was quoted as saying.

"We found two novel cancer genes that control blood vessel formation which are mutated in this cancer and which could be targeted for treatment of this highly aggressive cancer."

However, in some patients, the team found multiple mutations in the pathway that controls blood vessel growth. These multiple mutations may make drugs developed for a single target ineffective in some patients.

The study emphasises the need to take into account the effects multiple, cooperating mutations can have when designing targeted treatments for patients.

"This indicates that we may need to think more broadly to find a suitable treatment," adds Dr Campbell.

"This study really highlights the power that a limited number of samples can have to influence the clinical and biological understanding of a rare disease, in this case angiosarcoma," said Professor Adrian Harris of Oxford University and co-lead author.

"Not only does our study change the way people view the biology of this tumour, it acts as a guide for future drug trials in angiosarcoma patients."

Because so few people are affected by angiosarcoma, clinical trials can be very difficult to conduct. With this new information researchers now need to determine if existing drugs could be effective against this detrimental cancer.

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