(ChemotherapyAdvisor) – Modification of a tumor suppressor protein in glioblastomas leads to shortened survival times and drug resistance, according to an international team of researchers. This conclusion is based on a study entitled “Resistance to EGF receptor inhibitors in glioblastoma mediated by phosphorylation of the PTEN tumor suppressor at tyrosine 240,” which was published in the Proceedings of The National Academy of Sciences on August 13.
According to the investigators, glioblastoma multiforme (GBM), an aggressive brain cancer with a median survival time of 1 to 2 years, accounts for 20% of intracranial tumors in adults. This is a dreaded malignancy that does not have many effective treatment options. Even inhibitors of epidermal growth factor receptor (EGFR), which is overexpressed and/or mutated in ≥50% of GBM cases, are ineffective. GBM tumors can also become resistant to these inhibitors by unknown mechanisms. In this study, the investigators aimed to elucidate the mechanisms of resistance to EGFR inhibitors.
To meet this aim, the investigators focused on detecting the biochemical modification of cancer-associated genes. They found that PTEN, a tumor suppressor, is modified through a process known as phosphorylation. This event was observed in GBM clinical samples, suggesting its association with tumorigenesis. More importantly, the investigators also reported that phosphorylation of PTEN is associated with shortened overall survival and resistance to EGFR inhibitors.
Based on these findings, the investigators concluded that PTEN phosphorylation may be used as a biomarker to predict the response of GBM tumors to EGFR inhibitors.