The functional imperative in high-grade glioma

Precision oncology has emerged as a promising strategy for treating high-grade gliomas, yet its clinical impact has been disappointing, with over 300 clinical trials on targeted therapies failing to yield substantial improvements in patient outcomes. Current approaches primarily focus on static, marker-driven tumor features, which capture only a small portion of the complex biology that governs therapeutic responses. Functional precision oncology (FPO) offers a complementary approach, enhancing treatment selection in a personalized manner by dynamically testing patient-derived tumor cells against a range of available therapeutic agents. Here this review examines both historical and contemporary treatment strategies for high-grade gliomas and explores underlying reasons for the limited success of multiple precision oncology initiatives. We demonstrate how the incorporation of FPO in the armamentarium of glioma therapies may address these challenges and outline its proposed role as well as the practical considerations in utilizing FPO for clinical decision-making in patients with glioma.