Redundancy in Growth Factor Receptor Signaling in Adult Astrocytoma Resistance to Small-Molecule Tyrosine Kinase Inhibitors

Adult astrocytomas, particularly IDH1/IDH2-wildtype infiltrating astrocytic gliomas, represent a significant challenge for medical professionals. Despite recent progress in understanding tumor biology and the use of molecular biomarkers, therapeutic options have not significantly improved patient outcomes. Although targeted therapies, such as small-molecule tyrosine kinase inhibitors (TKIs), have shown benefits in other solid tumors, they have largely failed to improve survival in adult astrocytoma patients. Characterized by remarkable heterogeneity, these tumors develop robust drug resistance mechanisms. The molecular processes driving this resistance are complex and not yet fully understood. In this review, we briefly present the growth factor receptors (GFRs) and their signaling pathways in adult astrocytomas and discuss the known mechanisms of resistance to small-molecule tyrosine kinase inhibitors.