Biological tags on tumour blood vessels could provide new therapeutic targets
Tumours have a nasty habit of quickly developing their own blood supply in order to feed their rapid growth. Now, US researchers have discovered a set of biological markers that distinguish tumour-specific blood vessels from normal, healthy vasculature.
Brad St Croix and colleagues at the National Cancer Institute in Frederick, Maryland, studied mouse liver blood-vessels, and generated a full genetic profile of blood vessel formation (angiogenesis). Mouse livers have a capacity to regenerate, so the team was able to use cells from normal, cancerous and regenerating livers.
St Croix’s team used a genetic sequencing technique called Sage (serial analysis of gene expression), to clone and amplify short sections of RNA. ’This is the first time this problem has been approached in an unbiased study in this way - looking at all the genes expressed at the same time rather than just the specific genes of interest,’ St Croix told Chemistry World.
His team identified one particular cell surface receptor, CD276, which they confirmed was a marker of cancerous angiogenesis in humans. They now hope to formulate an antibody therapy based on their findings.
Angiogenesis is already a prime target for cancer treatments, but there are few effective anti-angiogenic drugs in clinical use. Roger Laham from Harvard Medical School in the US says that many prospective treatments had not translated successfully from animal models into humans and that, like many cancer drugs, they often caused collateral damage, leading to unpleasant side effects.
Current therapies target angiogenesis in general, so they also inhibit wound healing, Laham told Chemistry World. ’Patients who need to undergo surgery whilst on their cancer therapy would have to wait a while before they could go back onto these treatments. But if this research is confirmed, it could lead to anti-angiogenic drugs that target tumours exclusively.’
According to Laham, this systematic study supports the long held belief that pathological (disease-related) angiogenesis is very different from physiological angiogenesis. ’This confirms the gut feelings of many clinical researchers in the field,’ he said.
Cancer researchers acknowledge that there is no magic bullet solution to cancer, but the first anti-angiogenics fuelled a great deal of interest. St Croix might now have provided the key to the next generation of these treatments. ’Directing treatment at blood vessels has many advantages,’ said St Croix. ’It’s like cutting off the vine that feeds the whole bunch of cells - you can target them all at once.’
et al, Cancer Cell