Cancer drugs that aim to shrink tumours by cutting blood supply can actually help them SPREAD
Cancer drugs that shrink tumours by cutting off their blood supply may end up helping them to spread, a study suggests.
Drugs such as Glivec and Sutent reduce the size of tumours but could also make them more aggressive and mobile, it is claimed.
A little-studied group of cells called pericytes that provide structural support to blood vessels act as 'gatekeepers' to pen in cancer, scientists have discovered.
Sutent is one of two drugs which research suggests could make tumours more aggressive and mobile
Pericytes are wiped out by some advanced cancer drugs that prevent the growth of tumour-nourishing blood vessels, the research shows.
As a result tumours find it easier to 'metastasise', or spread around the body.
Tests on mice showed that both Glivec and Sutent depleted pericytes by 70 per cent while metastasis rates tripled.
Glivec, the brand name of the drug imatinib, and Sutent (sunitinib) have both been shown in trials to increase patient survival by a significant degree.
However, the research raises the possibility that ultimately they might help cancers become more deadly. Metastasis to vital organs such as the liver or brain is the chief reason why people die from cancer.
The US scientists, whose work is reported in the journal Cancer Cell, began by removing pericytes from breast cancer tumours in genetically engineered mice.
Glivec, the brand name of the drug imatinib, and Sutent (sunitinib) are used to fight human cancer cells (pictured)
They saw a 30 per cent decrease in tumour volumes over 25 days, but also a three-fold increase in the number of secondary tumours growing in the animals' lungs.
'If you just looked at tumour growth, the results were good,' said lead researcher Professor Raghu Kalluri, from Harvard Medical School in Boston. 'But when you looked at the whole picture, inhibiting tumour vessels was not controlling cancer progression. The cancer was, in fact, spreading.'
A closer look revealed a five-fold percentage increase in oxygen-starved 'hypoxic' areas in tumours lacking pericytes.
Cancer cells respond to oxygen deprivation by launching genetic survival programmes, said Prof Kalluri. They become more mobile, passing through leaky blood vessel walls, and begin to behave like treatment-resistant stem cells.
Smaller tumours appeared to be shedding more cancer cells into the blood than larger tumours with a good supply of pericytes, the study showed.
The next step was to conduct experiments with Glivec and Sutent.
Glivec works through a number of pathways, one of which is to target a blood vessel growth-promoting protein called PDGFR beta. Sutent also targets PDGFR beta as well as a range of other growth-promoters called VEGFR proteins.
Mice with primary tumours were treated with both drugs. The same result was found: with the loss of pericytes, metastasis increased three-fold.
'We showed that a big tumour with good pericyte coverage is less metastatic than a smaller tumour of the same type with less pericyte coverage,' said Prof Kalluri.
To see how relevant the findings were to patients, the scientists went on to examine 130 human breast cancer samples.
Samples with low numbers of pericytes in tumour blood vessel networks correlated with the most deeply invasive cancers, distant cancer spread, and five and 10-year survival rates lower than 20 per cent.
Some assumptions about cancer must now be revisited, Prof Kalluri believes.
'We must go back and audit the tumour and find out which cells play a protective role versus which cells promote growth and aggression,' he said.
'Not everything is black and white. There are some cells inside a tumour that are actually good in certain contexts.'