Researchers have identified 10 tumor-specific potential drug targets for the brain tumor glioblastoma. The results are presented in the scientific journal Cell Reports.

"We have found disease-related changes in the cells that line the tumor blood vessels, so called endothelial cells, which have long been considered a possible clinical target for cancer treatment," says the study lead. "Proteins only expressed in the endothelial cells of the tumor vessels could be used as targets to attack the tumor's blood supply, or for delivery of therapeutic agents, without affecting the normal brain."

There are more than 200 different cell types in the human body, each performing their own role. Understanding the differences between these cell types helps us understand how organs work and how cells change in disease. Cell identity is determined by the specific proteins expressed, which can be predicted by measuring the protein transcripts found inside the cell. For the study, the researchers analysed human brain tissue and samples of the brain tumor glioblastoma, an incurable disease with a very high mortality rate.

Existing data on transcripts from whole human brain tissue has limited usefulness when one is interested in the properties of a particular cell type, as these samples contain many different brain cell types. Now, the researchers have developed a new method to process this data and identify transcripts only expressed in certain types of brain cells. The method proved to be useful for defining cell-type properties, as well as directly comparing cell-type profiles between normal and diseased tissue.

The authors compared endothelial cell-enriched gene profiles with astrocyte, oligodendrocyte, neuron, and microglial cell profiles. Endothelial changes in malignant disease are explored using RNA-seq data from 516 lower-grade gliomas and 401 glioblastomas. Lower-grade gliomas appear to be an “endothelial intermediate” between normal brain and glioblastoma.

The researchers used this method to predict 10 novel glioblastoma-specific endothelial cell transcripts, which are not found in the vasculature of normal brain tissue.

"These markers could provide insights into the biology of glioblastoma and represent potential tumor-specific targets for therapy," says the author.

https://www.cell.com/cell-reports/fulltext/S2211-1247(19)31292-6

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