The image on the left shows a blood vessel in a tumour, with irregularities such as openings through which cancer cells can escape to other organs. The image on the right shows a blood vessel in a tumour with the sugar metabolism blocked. This blood vessel looks normal again, so that it becomes more difficult for cancer cells to spread and the cancer treatment is more effective.

Researchers led by Peter Carmeliet (KU Leuven-VIB) have found a novel way to normalize the dysfunctional blood vessels that are typical of tumours. These vessels play a pivotal role in cancer metastasis, as their fragility and permeability allows cancer cells to escape through the blood stream and invade other organs.

By manipulating the sugar metabolism of the blood vessel cells, the scientists were able to ‘cool down’ the overheated engines of the cells and create a healthy and structured blood vessel network. On top of preventing the spread of cancer cells, the restored vessels delivered chemotherapy drugs to the tumour in a more efficient way.

Blood vessel cells in tumours need to divide rapidly and therefore consume large quantities of sugar. As a result, the metabolism of these cells gets overheated, which makes them fragile, dysfunctional, and irregular in shape and size. Because of the weaknesses of flawed vessels, cancer cells can use them as ‘highways’ to spread to distant organs. Furthermore, they are unable to deliver enough oxygen to the tumour, which allows the tumour to proliferate even further. Finally, poorly functioning vessels hinder the smooth delivery of chemo- and immunotherapy drugs to the tumour.

Normal blood vessel cells need sugar to form new blood vessels. Blood vessels formed in tumours grow very quickly. This study shows that the blood vessel cells need large amounts of sugar to grow, so that their metabolism gets overheated. This leads to fragile and flawed blood vessels. The researchers managed to block the sugar metabolism, resulting in stronger blood vessels. This makes it more difficult for the cancer cells to escape and more easy for chemotherapy to reach the tumour.

Blocking sugar consumption

Whereas traditional cancer therapy tries to block new tumour blood vessel formation and destroy existing tumour vessels, the research team led by professor Peter Carmeliet focused on normalizing the detrimental process instead.

“Therapies that destroy tumour vessels are not always effective,” Professor Carmeliet explains. “In some cases, patients even show resistance to these drugs. So when we investigated the root of the problem, we were pleased to see that dysfunctional vessels are very susceptible to drugs blocking their sugar metabolisms, precisely because their sugar engines are so overheated. Our study proves that we can neutralize this out-of-control sugar consumption with a small molecule compound, thereby healing the impaired tumour vessels.”

Apart from reducing the chances of cancer cells spreading throughout the body, a future vessel normalization therapy would have other advantages as well. It could improve standard chemotherapy and provide extra benefits to recently developed immunotherapy.

“Our study also shows that healthy tumour vessels ensure a better delivery of chemotherapeutic agents to the tumour,” Professor Carmeliet continues. “They could also improve the supply of immune cells. This is very important, because many emerging cancer therapies directly address the body’s immune system. That is why we are already planning to investigate the effects of tumour vessel normalization therapy with immunotherapy. In this way, we are getting closer to identifying more targeted and specific treatments in the fight against cancer.”

Click here to read the study in Cancer Cell

Source: KU Leuven and VIB (with minor adaptations)