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Antiangiogenic strategies in medulloblastoma: reality or mystery
Fabio Grizzi1, Christina Weber, Antonio Di Ieva
1Laboratories of Quantitative Medicine, Istituto Clinico Humanitas IRCCS, 20089 Rozzano, Milan, Italy. fabio.grizzi@humanitas.it
Abstract:
Medulloblastoma is the most common malignant brain tumor of childhood. Surgery, radiation therapy, and chemotherapy successfully cure many patients, but survivors can suffer long-term toxicities affecting their neurocognitive and growth potential; furthermore, there is no curative therapy in up to 30% of cases, mainly because of our incomplete understanding of many of the underlying molecular and cellular processes. Angiogenesis is a hallmark of the progression of medulloblastoma and, over the last years, investigators have sought to develop effective and less toxic antiangiogenic strategies, including the inhibition or destruction of abnormal blood vessels using either antiangiogenic or vascular disrupting agents. However, the results are conflicting principally because of the complex biology of tumor vasculature and the irregular geometry of the vascular system in real space. In addition, current targets of antiangiogenic therapy, such as vascular endothelial growth factor (VEGF), are thought to be critical for both physiologic and pathologic angiogenesis, and clinical side effects of anti-VEGF therapy are beginning to emerge. We here review the state-of-the-art concerning antiangiogenic targets for medulloblastoma treatment, and discuss the complexity of the vascular system that intrinsically limits the efficacy of current strategies.
Insights
Medulloblastoma, a common childhood brain tumor, has limited curative options due to complex tumor biology. Current anti-angiogenesis strategies face challenges from intricate tumor vasculature and vital target roles.
Area of Science:
- Pediatric Oncology
- Cancer Biology
- Tumor Microenvironment
Background:
- Medulloblastoma is the most common malignant pediatric brain tumor.
- Current treatments (surgery, radiation, chemotherapy) cause long-term toxicities and fail in up to 30% of cases.
- Incomplete understanding of molecular processes hinders curative therapies.
Purpose of the Study:
- To review current anti-angiogenic targets for medulloblastoma treatment.
- To discuss the complexities of tumor vasculature limiting treatment efficacy.
- To explore less toxic therapeutic strategies.
Main Methods:
- Review of state-of-the-art anti-angiogenic targets.
- Analysis of medulloblastoma tumor biology and vascular system complexity.
- Discussion of vascular disrupting agents and anti-angiogenic strategies.
Main Results:
- Angiogenesis is a key feature of medulloblastoma progression.
- Anti-angiogenic strategies show conflicting results due to complex tumor vasculature.
- Current targets like vascular endothelial growth factor (VEGF) are vital for normal and pathological angiogenesis, leading to side effects.
Conclusions:
- The complex biology of medulloblastoma vasculature intrinsically limits the efficacy of current anti-angiogenic strategies.
- Development of effective and less toxic treatments requires a deeper understanding of tumor vascularization.
- Novel therapeutic approaches are needed to overcome treatment resistance and reduce long-term toxicities.
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