An international team of researchers from the University of Geneva (UNIGE) and the Amsterdam UM have chosen to control vascularization of tumors by intervening with cellular receptor that is specifically overexpressed in blood vessels of cancer.
By acting on the development of the blood vessels within the tumor, scientists hope to modulate vasculature and deliver the treatments extremely accurately, and even if necessary «cut the food» to the tumor, much like you would close a tap. These findings are published in the British Journal of Cancer
‘Direct attack of cancer cells could lead to the emergence of resistance. Regulating the vascularization of cancer cells could stop cancer cell growth.’
The Swiss and Dutch researchers have studied the mechanisms underlying the growth of new blood vessels inside tumors. In doing this they stumbled on the overexpression of the receptor that normally serves as the receptor for insulin, in the vasculature within the tumor. This finding may pave the way for developing a targeted treatment for cancer.
From a genomic screen we have discovered the role of this receptor, called the insulin receptor (INSR), mainly represented by the shorter oncofetal and non-metabolic isoform A(INSR-A), in the process of blood vessel formation. A molecule specifically targeting this receptor may allow us to modulate tumor growth or even completely block it» says Patrycja Nowak-Sliwinska, assistant professor in the School of Pharmaceutical Sciences of the Faculty of Sciences of UNIGE and first author of the study.
After many years of investigations, the researchers were able to confirm this discovery in both in vitro and in vivo experiments. They now hope to develop a specific molecule, with the help of an industrial partner.
Comparisons on eleven tumor types
One of the strengths of this research is its ability to precisely target the tumor endothelium, the innermost layer of blood vessels in contact with the blood, while sparing healthy cells. To ensure this, the researchers compared healthy and diseased tissue sections for eleven different types of tumors, such as kidney, colon or breast. The importance of insulin receptors as a target for cancer treatment highlighted by this research also lies in the indirect approach of the disease.
«When cancer cells are attacked directly, failure is common, as each procedure can lead to a change in the tumor's behavior. They are genetically unstable and may mutate into drug resistant variants. We need to outsmart cancer cells», commented Arjan W. Griffioen, the head of Angiogenesis Laboratory at the Amsterdam UMC, location VUmc.
By intervening with endothelial cells and targeting the vascularization for which they are responsible, researchers avoid frontal attack on the tumor. «We do not act directly on cancer, but we found the valve that regulates the vascularization of cancer cells», conclude the researchers.