Targeting tumour blood vessels
Tumour cells require oxygen and nutrients to be able to grow and therefore a tumour induces the formation of new blood vessels. This process of formation of new blood vessels from pre-existing vasculature is called angiogenesis. Several anti-angiogenic drugs are currently available for the treatment of cancer. Most of them target the tumour’s angiogenic factors and their efficiency is often diminished by the development of resistance to treatment with these drugs. The aim of the EU-funded GENE(opens in new window) (Genomic screening of the embryo for novel targets in the tumour endothelium) was to find specific markers of tumour endothelial cells, the cells lining the inner of the tumour blood vessels, to be able to specifically target the tumour blood vessels with drugs. The working hypothesis of the project was based on the idea that genes that are functional during embryonic development might be also active in the tumour vasculature. The researchers analysed the full expression profile of mouse embryos at different stages of development as well as that of tumour endothelial cells. They used adult mouse tissues for comparison to identify the genes that are specific for embryos. Screening identified 24 candidate genes, which had 100-fold higher expression in tumour endothelial cells in comparison to the adult mouse tissues. Researchers validated the tissue expression of the 10 most promising extracellularly expressed candidate genes. Research work by the GENE project represents an important initial stage of the development of novel and potentially highly efficient anti-cancer drugs. The identified targets are specific to the tumour endothelial cell, a feature which will minimise potential toxic side effects and reduces the possibility of tumour cell mutation into drug resistant variants.
