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Published on: September 1, 2018
Stem cell-mediated gene therapies for malignant gliomas: a promising targeted therapeutic approach?
Ghazaleh Tabatabai1, Wolfgang Wick, Michael Weller
1Laboratory of Molecular Neurooncology, University of Zurich, Switzerland.
Abstract:
Glioblastomas are aggressive intrinsic brain tumors. The median overall survival does not exceed 15 months despite surgical resection, radiotherapy, and chemotherapy even in selected clinical trial populations. One reason for this poor outcome is the characteristic infiltrative growth pattern of glioblastomas with tumor cells deeply infiltrating into the normal brain parenchyma and thereby escaping surgical debulking and involved-field radiation therapy. Novel therapeutic strategies are urgently needed including those that target disseminated tumor cells, too. In this regard, the application of adult stem cells as cellular vehicles for the delivery of therapeutic molecules has emerged during the last decade as an experimental approach. Adult stem cells with a tropism for gliomas include neural stem and progenitor cells, mesenchymal stem cells, hematopoietic progenitor cells, and endothelial progenitor cells. Importantly, these candidate cellular carriers also localize to sites of hypoxia and invasive tumor borders which are usually not targeted by currently available therapeutic approaches. Stem cell-based therapeutic approaches could therefore help to overcome some of the current limitations of radio- and chemotherapy and may circumvent toxicity to normal resident cells of the central nervous system. The development of neural stem- and progenitor-based therapies is advanced with a currently ongoing phase I clinical study. We review rationale, achievements, and future challenges in this field.
Insights
Adult stem cells offer a promising new strategy for treating glioblastomas, an aggressive brain tumor. These cells can target invasive tumor cells, potentially improving survival rates beyond current treatments.
Area of Science:
- Neuro-oncology
- Stem Cell Biology
- Cancer Therapeutics
Background:
- Glioblastomas are highly aggressive brain tumors with poor prognoses.
- Current treatments (surgery, radiation, chemotherapy) have limited efficacy due to infiltrative tumor growth.
- Disseminated tumor cells and invasive borders remain challenging to target effectively.
Purpose of the Study:
- To review the rationale, achievements, and challenges of using adult stem cells for glioblastoma therapy.
- To explore stem cells as cellular vehicles for delivering therapeutic agents.
- To highlight the potential of stem cell-based approaches to overcome current treatment limitations.
Main Methods:
- Review of existing literature on adult stem cell tropism for gliomas.
- Analysis of stem cell localization to hypoxic regions and invasive tumor borders.
- Examination of ongoing clinical studies, including a Phase I trial for neural stem and progenitor cell therapies.
Main Results:
- Several adult stem cell types (neural, mesenchymal, hematopoietic, endothelial progenitor cells) show tropism for gliomas.
- These stem cells can localize to critical tumor sites often missed by conventional therapies.
- Stem cell-based approaches show potential to circumvent CNS toxicity associated with current treatments.
Conclusions:
- Adult stem cells represent a promising experimental approach for glioblastoma treatment.
- Targeting disseminated cells and invasive borders with stem cells could improve therapeutic outcomes.
- Further development and clinical evaluation are necessary to realize the full potential of stem cell-based glioblastoma therapies.
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