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Recurrent high-grade glioma: a diagnostic and therapeutic challenge
Tobias Walbert1, Tom Mikkelsen
1Department of Neurosurgery, Hermelin Brain Tumor Center, Henry Ford Health System, 2799 W Grand Blvd, Detroit, MI 48202, USA.
Abstract:
The management of recurrent high-grade gliomas with conventional, as well as targeted, therapies is problematic owing to several confounding issues. First, the diagnosis of recurrence using MRI is not straightforward, making the assessment of images in daily routines, as well as in clinical trials, challenging. While chemotherapies with cytotoxic agents have demonstrated initial treatment response, most tumors recur quickly. Second, targeted therapy itself is confounded by the heterogeneous expression of drug targets and nonlinear signaling effects, with functional redundancy and sidestream feedback mechanisms resulting in treatment failure; however, several active agents have been identified, most notably, bevacizumab (an antibody that sequesters VEGF), cilengitide (an inhibitor of integrin αvβ3/5 signaling) and cediranib (an oral tyrosine kinase inhibitor targeting PDGF receptor, c-Kit and all VEGF receptor subtypes). All of these agents have undergone multiple clinical trials and have demonstrated benefits and progression-free survival prolongation in recurrent disease. Given these advances, it is likely that tailored therapies for tumors harboring specific signaling defects will become more efficient and successful in the management of glioblastoma.
Insights
Managing recurrent high-grade gliomas is difficult due to diagnostic challenges and treatment resistance. Targeted therapies like bevacizumab show promise for extending progression-free survival in recurrent gliomas.
Area of Science:
- Neuro-oncology
- Molecular targeted therapy
- Medical imaging
Background:
- Recurrent high-grade gliomas present significant management challenges.
- Magnetic resonance imaging (MRI) diagnosis of recurrence is often ambiguous.
- Conventional chemotherapies show limited long-term efficacy due to rapid tumor recurrence.
Purpose of the Study:
- To review the challenges in managing recurrent high-grade gliomas.
- To discuss the potential of targeted therapies in overcoming treatment resistance.
- To highlight recent advances in targeted agents for glioblastoma.
Main Methods:
- Review of current literature on glioma recurrence management.
- Analysis of clinical trial data for targeted agents.
- Discussion of diagnostic limitations in MRI assessment.
Main Results:
- Targeted agents, including bevacizumab, cilengitide, and cediranib, have shown benefits.
- These agents demonstrated progression-free survival prolongation in recurrent disease.
- Tumor recurrence is often linked to heterogeneous target expression and signaling pathway redundancy.
Conclusions:
- Targeted therapies offer improved outcomes for recurrent gliomas.
- Tailored treatments addressing specific signaling defects are crucial for glioblastoma management.
- Advances in targeted therapy are enhancing the efficacy of recurrent glioma treatment.
