RB1 and central nervous system cancer: To date, three core signaling pathways have been identified for high-grade glioma, namely, the receptor tyrosine kinase (RTK)/phosphatidylinositol 3'-kinase (PI3K)/alpha serine-threonine protein kinase (AKT), phosphoprotein53 (TP53), and retinoblastoma (RB1) signaling pathways 14-16.