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Functional Precision Oncology: The Next Frontier to Improve Glioblastoma Outcome?
Dena Panovska1, Frederik De Smet1
1Department of Imaging and Pathology, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.
Abstract:
Glioblastoma remains the most malignant and intrinsically resistant brain tumour in adults. Despite intensive research over the past few decades, through which numerous potentially druggable targets have been identified, virtually all clinical trials of the past 20 years have failed to improve the outcome for the vast majority of GBM patients. The observation that small subgroups of patients displayed a therapeutic response across several unsuccessful clinical trials suggests that the GBM patient population probably consists of multiple subgroups that probably all require a distinct therapeutic approach. Due to extensive inter- and intratumoral heterogeneity, assigning the right therapy to each patient remains a major challenge. Classically, bulk genetic profiling would be used to identify suitable therapies, although the success of this approach remains limited due to tumor heterogeneity and the absence of direct relationships between mutations and therapy responses in GBM. An attractive novel strategy aims at implementing methods for functional precision oncology, which refers to the evaluation of treatment efficacies and vulnerabilities of (ex vivo) living tumor cells in a highly personalized way. Such approaches are currently being implemented for other cancer types by providing rapid, translatable information to guide patient-tailored therapeutic selections. In this review, we discuss the current state of the art of transforming technologies, tools and challenges for functional precision oncology and how these could improve therapy selection for GBM patients.
Insights
Glioblastoma (GBM) is a resistant brain tumor. Functional precision oncology offers a new strategy to tailor treatments by testing therapies on individual patient tumor cells.
Area of Science:
- Neuro-oncology
- Cancer Biology
- Translational Medicine
Background:
- Glioblastoma (GBM) is a highly malignant and treatment-resistant adult brain tumor.
- Despite decades of research and numerous identified targets, clinical trials have largely failed to improve patient outcomes.
- Tumor heterogeneity complicates personalized treatment strategies, limiting the effectiveness of traditional genetic profiling.
Purpose of the Study:
- To review the current advancements, technologies, and challenges in functional precision oncology for Glioblastoma.
- To explore how functional precision oncology can improve therapy selection for GBM patients.
Main Methods:
- Discussion of emerging technologies and tools for functional precision oncology.
- Analysis of ex vivo evaluation of living tumor cells for treatment efficacy and vulnerability assessment.
- Review of approaches applied to other cancer types for guiding patient-tailored therapeutic selections.
Main Results:
- Small patient subgroups showing therapeutic responses in past trials suggest distinct GBM subtypes requiring tailored approaches.
- Functional precision oncology provides a personalized method to evaluate treatment effectiveness on individual tumor cells.
- This approach offers rapid, translatable information for guiding therapeutic decisions.
Conclusions:
- Functional precision oncology represents a promising strategy to overcome GBM heterogeneity and improve treatment selection.
- Personalized ex vivo testing of therapies on patient tumor cells can lead to more effective GBM treatment strategies.
- Further development and implementation of these methods are crucial for advancing GBM patient care.
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