A study by Children’s Cancer Institute researchers has provided an important piece of the jigsaw puzzle in the search for a better way to treat high-grade glioma, the second most commonly diagnosed brain cancer in children, which has a dismal 5-year survival rate of less than 20%.
In the quest for an effective treatment for this devastating disease, researchers in the Institute’s Therapeutic Discovery Theme have been working to find new therapeutic targets — molecules in the glioma cells that can be targeted by therapeutic agents, particularly immunotherapies.
While immunotherapies have been used to great effect in certain cancers, this has not been the case for high-grade glioma so far. One of the main reasons for this is that it has proven difficult to find targets that are unique to the tumour cells and not present on healthy brain cells.
‘We need to find cancer-selective therapeutic targets in high-grade glioma,’ explained Research Officer Dr Alexis Minchaca Acosta, lead author on the study, which was published in the Journal of Proteome Research. ‘To do this, we’ve been trying to identify unusual features on the surface of these tumour cells — external markers on the cell membrane that are rarely found on normal cells.’
Traditionally, cancer researchers have focused their attention on well-known cell surface proteins. However, this approach does not take into account that other proteins can move from elsewhere in the cell to appear on the cell surface.
In the current study, a technique known as surfaceome analysis was used to examine membrane proteins in high grade glioma cells, finding that several proteins known as endoplasmic reticulum (ER) chaperones move to the surface of these cells, despite not traditionally residing in the cell membrane.
‘Identifying cell membrane markers by studying the surfaceome specifically can help us find novel antigens,’ commented senior author, Dr Angelica Merlot. ‘Analysis of mRNA and bulk proteomics does not always correctly predict or correlate to membrane expression.’
‘By studying the surfaceome, we are expanding the landscape of potential targets for the development of immunotherapies against high grade glioma.’
Full publication: https://doi.org/10.1021/acs.jproteome.5c00616
