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The functional imperative in high-grade glioma
Laura Shih Hui Goh1,2,3, Dexter Kai Hao Thng2, Yvonne Li En Ang4
1Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Abstract:
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.
Insights
Functional precision oncology (FPO) offers a personalized approach to treating high-grade gliomas by testing patient tumor cells against therapies. This method aims to overcome the limitations of current precision oncology strategies for improved patient outcomes.
Area of Science:
- Neuro-oncology
- Cancer Biology
- Translational Medicine
Background:
- Precision oncology for high-grade gliomas has shown limited clinical success despite numerous trials.
- Current strategies rely on static tumor markers, failing to capture complex biological responses to therapy.
Purpose of the Study:
- To review historical and current high-grade glioma treatments.
- To explore reasons for precision oncology's limited impact.
- To introduce Functional Precision Oncology (FPO) as a complementary approach.
Main Methods:
- Review of existing literature on high-grade glioma treatments.
- Analysis of precision oncology trial outcomes.
- Conceptual framework for integrating FPO into clinical practice.
Main Results:
- Over 300 clinical trials targeting static markers have not significantly improved outcomes.
- FPO dynamically tests patient-derived tumor cells against various agents for personalized treatment selection.
- FPO addresses the limitations of static marker-driven approaches.
Conclusions:
- Functional Precision Oncology (FPO) presents a promising strategy to enhance personalized treatment selection for high-grade gliomas.
- Integrating FPO may overcome challenges in current precision oncology initiatives.
- Practical considerations for implementing FPO in clinical decision-making are outlined.
