Gene

GENE

Genomic screening of the Embryo for Novel targets in the tumor Endothelium

 

Contact

e.huijbers@vumc.nl

Explanation

Endothelium

The cells that form the inner lining of the blood vessels.

Extracellular matrix

sturcture to which cells adhere

In vitro

in cell culture

Marie Curie Actions -

Intra-European Fellowship

 

FP7-PEOPLE-2012-IEF

 

 

Angiogenesis

 

Angiogenesis is the formation of new blood vessels form pre-existing vasculature. This occurs in the healthy body during wound healing or the growth of the endometrium. However, under pathological conditions abnormal angiogensis may occur. An example is the excess of angiogenesis in cancer (tumor growth).

Staining of mouse

tumor tissue

green: blood vessel

red: extracellular matrix

blue: nuclei

In the 1970's the idea was born that tumor growth can be inhibited by targeting angiogenesis. Blocking tumor blood vessel growth deprives the tumor cells of nutirients and oxygen. Today there are several angiogensis inhibitors on the market for treatment of cancer. Most of these drugs target pro-angiogenesis signaling by tumor cells through neutralization of growth factors (e.g. anti-VEGF (vascular endothelial growth factor) antibodies like bevacizumab/Avastin), or by inhibiting kinase activity of the growth factor receptors (e.g. sunitinib/Sutent). Although these drugs experience (commercial) success, it is now becoming evident that these agents, in general, only have a moderate effect on survival rates of patients. Furthermore, these angiogenesis inhibitors show severe side effects in patients.

Specific targeting of the tumor blood vessels

We would like to develop a better and more specific anti-angiogenic therapy. Therefore, our approach is to identify novel specific markers of angiogenic tumor endothelium, which we can target with specific drugs. Advantages would be that this approach is independent of the growth factor production by tumor cells, reducing the risk of tumor cell mutation into drug resistant variants. In addition, if the identified targets are specific to the tumor endothelial cells, toxic side effects would be minimized.

Search for specific targets in the tumor blood vessels

Our idea is that certain genes with an exclusive function in the embryo also become expressed in the tumor vasculature. We have indeed identified several embryonic genes, which are switched on in tumor endothelial cells again, but are not present in the adult. Currently, we are performing target function experiments in vitro.

GOAL

Identification of new targets in the tumor blood vessels for the development of anti-angiogenic drugs.

 

Links

www.angiogenesis.nl

 

http://www.vumc.com/branch/cca/

 

 

Cancer Center Amsterdam

Inhibition of angiogenesis as a strategy to inhibit tumor growth

Disclaimer: E. Huijbers, updated 15 October 2014