Restoring flawed tumor blood vessels may offer better cancer treatments

Emobileclinic Researchers Corner

The Journal of Cancer Cell has published the findings of researchers led by Dr Peter Carmeliet who discovered a new way to normalize the dysfunctional blood vessels that are typical for tumors. According to them, those vessels has significant role in cancer metastasis, as their fragility and permeability enables cancer cells to pass through the blood stream and fight other organs.

The researchers were able to reduce the actions of these cancers by manipulating the blood vessel cells’ sugar metabolism which enables them to establish a healthy and structured blood vessel network. Apart from averting the spread of cancer cells, the restored vessels produced chemotherapy drugs in a more efficient way to the tumor.
Blood vessel cells also known as endothelial cells, in tumors have to divide quickly and hence need large quantities of sugar. As a result, the metabolism of those cells become overheated, which in turn render them fragile, dysfunctional and irregular in shape and size. As a result of the weaknesses of flawed vessels, cancer cells use them as a platform to proliferate to far organs. Furthermore, they are unable to provide adequate oxygen for the tumor, which enables the tumor to spread even further. Lastly, poorly-functioning vessels impede the smooth delivery of chemo- and immunotherapy drugs to the tumor.

In contrast to the traditional cancer therapy aimed at obstructing new blood vessel tumor emergence and destroying existing tumor vessels, the research team led by Professor Peter Carmeliet (VIB-KU Leuven) focused on normalizing the inimical process instead.

According to the team leader, “therapies that destroy tumor vessels are not always effective. 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 could neutralize this out-of-control sugar consumption with a small molecule compound, thereby healing the impaired tumor vessels.”

Apart from minimizing the probability of cancer cells proliferation of the entire body, a future vessel normalization therapy has other perks as well. As a matter of fact, it offers not only improved chemotherapy standard but also created an extra benefits to recently developed immunotherapy.

The team leader further said: “our study also shows that healthy tumor vessels ensure a better delivery of chemotherapeutic agents to the tumor. In addition, they could improve the supply of immune cells as well. 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 tumor vessel normalization therapy with immunotherapy. In this way, we are getting closer to identifying more targeted and specific treatments in the fight against cancer.”

Source

Cantelmo, A. R et.al (2016): Inhibition of the Glycolytic Activator PFKFB3 in Endothelium Induces Tumor Vessel Normalization, Impairs Metastasis, and Improves Chemotherapy. Cancer Cell, doi: 10.1016/j.ccell.2016.10.006