It is the single most mutated kinase in glioblastoma, the most malignant primary brain tumor.[22] The PtdIns(3,4,5)P3 phosphatase PTEN that antagonises PI3K signaling is absent from many tumours. In addition, the epidermal growth factor receptor EGFR that functions upstream of PI3K is mutationally activated or overexpressed in cancer.[22][23] Hence, PI3K activity contributes significantly to cellular transformation and the development of cancer.