IL13RA2 in GBM: Expression dynamics with targeted treatment
Targeted therapies are a promising alternative to standard cancer treatment. In the case of glioblastoma, a deadly brain tumor, the Il13Ra2 receptor has become a significant target for these therapies due to its overexpression in GBM patients. However, early clinical trials have shown that patients often experience disease progression after an initial response period to Il13Ra2-targeted therapies. This progression may be due to developed resistance from exposure to the treatment through mechanisms such as clonal selection. Clonal selection suggests that Il13Ra2-targeted treatment eliminates cells with high expression of Il13Ra2, leaving lower or non-expressing clones to proliferate. The research project aims to investigate this mechanism by assessing Il13Ra2 expression in GBM cells treated with GB13, an endotoxin-conjugated ligand for the receptor. Live cell imaging and cell counting confirmed that GBM43 cells treated at the IC50 experienced cell death within 72 hours. Detection of Cleaved Caspase 3 by western blot confirmed cell death in the first 72 hours. However, and unexpectedly, Il13Ra2 expression appeared to increase compared to the control and then remained constant during and after treatment. Immunofluorescence will be conducted to validate these findings. This analysis suggests that the influence of targeted therapies on membrane expression and drug-resistance over time may be more complicated than the formerly proposed clonal selection. Future research should explore the sensitivity of the cell due to upregulation and the consequences of multi-drug treatment.
