A study revealed that some anti-cancer drugs can cause not only hypertension issues but also the rupture of blood vessels and severe cardiovascular problems.
Researchers from the National Center for Oncological Research (CNIO) in collaboration with researchers from the National Center for Cardiovascular Research (CNIC), conducted a study published in the journal Nature Medicine, in which they have linked the use of the recently FDA approved inhibitors of Plk1 as “Therapy Innovative in Leukemia ” with the onset of cardiovascular problems.
In particular, the study suggests that the prolonged use of these inhibitors can produce not only hypertension, but also the rupture of blood vessels and severe cardiovascular problems.
In recent years inhibitors of cell cycle regulators – the process that controls the proliferation of tumor cells – have shown their usefulness in the fight against various tumors such as breast cancer.
WHICH PRODUCTS MAY CAUSE PROBLEMS?
Among the new drugs that use this strategy is Volasertib. An inhibitor of the Plk1 protein that has shown very promising results in the treatment of Acute Myeloid Leukemia.
«ONE OF THE PROBLEMS THAT WE ENCOUNTER WHEN TESTING NEW DRUGS IN PATIENTS IS THAT WE KNOW VERY LITTLE ABOUT THE REAL FUNCTION OF THE PROTEINS TO WHICH THESE DRUGS ARE AIMED AT» said Marcos Malumbres, study coordinator. His CNIO team wanted to study the actual function of the Plk1 protein in mammals using laboratory mice.
To study the function of Plk1, the researchers generated a mouse variant with decreased levels of that protein.
«IT WAS SURPRISING, HALF OF THE MICE DIED OF THORACIC HEMORRHAGE DUE TO THE RUPTURE OF THE ARTERIES» said Guillermo de Cárcer, CNIO researcher and the article’s first author.
«THE MALES DIED THE FIRST NIGHT THAT THEY SPENT IN THE SAME BOX WITH THE FEMALES »he added that «THIS IS ONE OF THE SITUATIONS THAT CAUSES THE HIGHEST RISE OF BLOOD TENSION IN YOUNG MALES»
Plk1 had initially been seen as a protein that controls how cells multiply. This caught the attention of pharmaceutical companies that saw in it a new therapeutic target to slow tumor growth. Several inhibitors of this protein are now in clinical trial phase for various types of tumors.
Volasertib, has recently been recognized as one of the best therapies against Acute Myeloid Leukemia. Like most chemotherapy drugs, Volasertib causes some side effects that are still under study.
A team of researchers that included Juan Miguel Redondo’s team (CNIC), as well as scientists from the Center for Cancer Research (CIC) of the University of Salamanca and the London Research Institute, treated mice with low doses of Volasertib for two months. Mice with low levels of Plk1 or treated with Volasertib had no growth problems. But they suffered from ruptured arteries and secondary heart problems.
Arteries are even more sensitive to the inhibition of Plk1 than other tissues in adult organisms. In fact, the study shows that Plk1 is an essential protein for the contraction of the cells that decorate the arteries’ wall. This is a cell movement that is responsible for maintaining blood pressure at adequate levels.
Cardiovascular problems and cancer are major causes of morbidity and mortality in advanced societies. The involvement of Plk1 in the control of both processes will have important repercussions in future biomedical developments.
Malumbres concludes that: “We have to study the biological function of the protein very well and utilize appropriate models before using it. Only then can we design protocols for patients that are both appropriate and with fewer side effects”.