We take a look at some of the latest findings from Breast Cancer Now scientist Dr Andrew Reynolds, who has been finding out how secondary tumours can ‘hijack’ existing blood vessels to help cancer cells survive and resist treatment.

Thursday 26 October 2017      Research blog
Scientist looking down a microscope

One of the greatest challenges that breast cancer researchers face is understanding how and why secondary tumours form and finding new ways to tackle them. Secondary tumours occur when cancer cells escape from the breast and travel to other sites in the body such as the lungs, liver, bones and brain. Although secondary breast cancer won’t affect every patient, when it does develop it is incurable.

What’s blood got to do with it?

Blood contains the oxygen and nutrients that all cells, including cancer cells, need to survive. As tissues and organs grow larger, so does their demand for oxygen; this leads to the growth of new blood vessels through a process known as angiogenesis. Scientists have previously found that tumours can also carry out angiogenesis to access a blood supply, which encourages tumour growth and may be key in enabling cancer cells to spread throughout the body and form secondary tumours. Anti-angiogenic drugs have been developed which can stop these new blood vessels from forming, however so far, they have had little success in improving outcomes for breast cancer patients.

Last year, Dr Andrew Reynolds, who until recently was based at the Breast Cancer Now Toby Robins Research Centre at the Institute of Cancer Research, published three papers which point to a potential cause of this resistance to anti-angiogenic drugs – called vessel co-option - where tumours ‘hijack’ existing blood vessels, rather than growing new ones.

Vessel co-option in the liver...

The first in Dr Reynolds’ trilogy of papers investigated how resistance to anti-angiogenic drugs can develop in advanced liver cancer. Dr Reynolds showed that, while anti-angiogenics were initially effective, cancer cells could undergo molecular changes that allow them to co-opt the existing blood vessels in the liver, making these drugs less effective. This paper was the first to demonstrate that blood vessel co-option could help cancers to resist anti-angiogenic treatments.

…and the lungs

Anti-angiogenic drugs, such as bevacizumab and sunitinib, have shown disappointing results in clinical trials for secondary breast cancer patients. The following two papers from Dr Reynolds explored why these drugs may be ineffective in treating secondary tumours in the liver and lungs respectively.

Through the analysis of secondary tumour samples, Dr Reynolds and his team confirmed that blood vessel co-option occurs in the liver and the lungs. These samples showed that secondary tumours have distinct ways of growing, which allow them to ‘piggyback’ on an existing blood supply. In the lungs, three distinct methods were identified that allow the tumours to co-opt blood vessels. They also found that tumours can grow using a combination of vessel co-option and angiogenesis.

Thanks to the research of Dr Reynolds and his team, we now have a good explanation as to why anti-angiogenic drugs showed a limited benefit in patients with breast cancer. It appears that breast cancers are able to find an alternative blood supply by hijacking pre-existing vessels, enabling the cancer cells to survive.

Targeting the tumour twice

So how can this research help breast cancer patients? By understanding the different ways that secondary tumours can take hold of a blood supply, researchers may be able to develop new treatments to target vessel co-option, which could be given alongside existing anti-angiogenic drugs. This two-pronged attack could both prevent new blood vessels from growing and stop tumours hijacking existing blood vessels, starving the cancer cells of the oxygen and nutrients they need to survive.