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Glioblastoma Therapy: Rationale for a Mesenchymal Stem Cell-based Vehicle to Carry Recombinant Viruses
Sakhawat Ali1, Qin Xia1, Tahir Muhammad2
1School of Life Science, Beijing Institute of Technology, Beijing, 100811, China.
Abstract:
Evasion of growth suppression is among the prominent hallmarks of cancer. Phosphatase and tensin homolog (PTEN) and p53 tumor-suppressive pathways are compromised in most human cancers, including glioblastoma (GB). Hence, these signaling pathways are an ideal point of focus for novel cancer therapeutics. Recombinant viruses can selectivity kill cancer cells and carry therapeutic genes to tumors. Specifically, oncolytic viruses (OV) have been successfully employed for gene delivery in GB animal models and showed potential to neutralize immunosuppression at the tumor site. However, the associated systemic immunogenicity, inefficient transduction of GB cells, and inadequate distribution to metastatic tumors have been the major bottlenecks in clinical studies. Mesenchymal stem cells (MSCs), with tumor-tropic properties and immune privilege, can improve OVs targeting. Remarkably, combining the two approaches can address their individual issues. Herein, we summarize findings to advocate the reactivation of tumor suppressors p53 and PTEN in GB treatment and use MSCs as a "Trojan horse" to carry oncolytic viral cargo to disseminated tumor beds. The integration of MSCs and OVs can emerge as the new paradigm in cancer treatment.
Insights
Reactivating tumor suppressors PTEN and p53, using mesenchymal stem cells (MSCs) to deliver oncolytic viruses (OVs), offers a novel strategy for glioblastoma treatment by overcoming current therapeutic limitations.
Area of Science:
- Oncology
- Virology
- Regenerative Medicine
Background:
- Cancer cells evade growth suppression, with PTEN and p53 pathways often compromised in glioblastoma (GB).
- Oncolytic viruses (OVs) show promise for selective cancer cell killing and gene delivery but face challenges like immunogenicity and poor tumor distribution.
- Mesenchymal stem cells (MSCs) possess tumor-homing abilities and immune privilege, making them suitable carriers for therapeutic agents.
Purpose of the Study:
- To advocate for reactivating p53 and PTEN tumor suppressors in glioblastoma (GB) treatment.
- To explore the use of mesenchymal stem cells (MSCs) as carriers for oncolytic viruses (OVs) in GB therapy.
- To highlight the potential of combining MSCs and OVs to overcome individual limitations and improve cancer treatment.
Main Methods:
- Reviewing existing findings on PTEN and p53 tumor suppressive pathways in glioblastoma (GB).
- Evaluating the application of oncolytic viruses (OVs) for gene delivery in GB models.
- Assessing the potential of mesenchymal stem cells (MSCs) to enhance OV delivery and targeting.
Main Results:
- PTEN and p53 pathways are critical targets for glioblastoma (GB) therapy.
- MSCs can serve as effective carriers ('Trojan horses') for oncolytic viruses (OVs).
- Combining MSCs and OVs can improve therapeutic efficacy by enhancing targeting and distribution.
Conclusions:
- Reactivating p53 and PTEN is a viable strategy for glioblastoma (GB) treatment.
- MSC-mediated OV delivery offers a promising approach to target disseminated tumors.
- The integration of MSCs and OVs represents a potential new paradigm in cancer therapy.
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