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Starving cancer might need a new approach

Cancer is a hungry beast. As tumour cells multiply, they need a constant supply of nutrients and oxygen, which they get from the extensive network of blood vessels coursing through our bodies. Tumours grow quickly and the cells innermost of the growing mass are at risk of being starved unless they can get access to the blood supply.

Tumours have adopted a clever strategy to protect themselves from starvation: they grow new blood vessels in a process called angiogenesis. These new blood vessels are nothing like their straight and narrow healthy cousins. They are a nest of twisting and haphazardly built pipes, snaking around and within the new tumour. The formation of new blood vessels has become so integral to cancer biology that it is now considered as a hallmark of cancer.

Based on this idea, scientists started developing drugs that would starve the tumour by stopping it from growing new blood vessels, and studies in mice confirmed that this was a treatment strategy worth pursuing. When treated with these drugs, called antiangiogenics, tumours shrivelled and disappeared. The drugs were taken into human trials, but results were disappointing. While some patients showed great responses to the new treatments, many, especially people whose cancer had spread (metastasised) throughout the body, fell way below what was expected.

A possible solution

Where had science gone wrong? Professor Robert Kerbel, a cancer researcher based at Sunnybrook Research Institute in Canada, is one of the scientists who thinks he has an explanation. In an article, published in the science journal Nature, Kerbel makes the case that researchers are using the wrong animal models to study angiogenesis, and we are only attacking half of the problem.

Kerbel says that research has shown that the mouse models used by researchers in the lab are not particularly good at recreating what is actually happening in human cancer. Most patients in clinical trials suffer from advanced cancer, a disease that has been through several rounds of treatment, metastasised and is now resistant to standard therapies. The mice on the other hand are often implanted with a squeaky clean and fresh new tumour. On top of that, the potential treatment is often only assessed in its effectiveness against a primary tumour, rather than secondary tumours that appear in other organs. And it is these secondary tumours that ultimately kill the patient, where vital organs like the liver, kidneys and lungs are affected.

Hijacking blood vessels

The second point Kerbel makes is that growing new blood vessels is not the only way a tumour can feed itself. Tumours also have the ability to hijack healthy blood vessels to feed off them. For years this process, called vessel co-option, has been overlooked. It might be the reason why antiangiogenic drugs haven’t worked particularly well. Kerbel and others have investigated different tumours and found that the growing of new blood vessels is far from the only, or in some tumours, even the main way of supplying nutrients. Kerbel studied more than 100 patient samples of metastasised cancer that had settled in their lungs and found that over 80% of the tumours had taken advantage of the body’s own blood supply, hijacking what already existed, rather than building a new network of pipes.

When cancer spreads it can often ends up in the lungs. These secondary tumours are particularly difficult to treat and this could be due to the fact that they are hijacking healthy blood vessels, rendering antiangiogenic drugs that stop growth of new blood vessels useless. In other cases, tumours might initially be sensitive to antiangiogenic treatment while they rely on their ability to grow new blood vessels but become resistant to the drugs over time as they switch to using the body’s own healthy blood vessels.

A new approach

This area of research has been overlooked for a shockingly long time, but now researchers are coming round and focusing their attention on the importance of vessel co-option. Kerbel suggests that the future of cancer treatment may lie in a combination of anti-angiogenic drugs and agents that stop vessel co-option. With funding from Worldwide Cancer Research Kerbel and his team are trying to find out how breast tumours, that have spread to the lungs, connect to the body’s own blood supply and how much of a tumour’s blood supply comes from its own newly built blood vessels versus the hijacked ones. They are hopeful that, based on these findings, they will be able to develop a new therapeutic approach that targets vessel co-option alongside existing antiangiogenics.

“The funding has allowed us to undertake investigations in an area of research which very few other labs around the world are working on, but which we think is going to be very important and may open up a whole new are of how to treat cancer by targeting the vasculature.” When asked if he had a message for our supporters, he said: “Thank you, thank you, thank you! These days it is difficult to get funding for research. I’m very grateful that Worldwide Cancer Research has funded this particular study.”

Read the original article: Vessel co-option in cancer, Nature Reviews Clinical Oncology, 2019

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