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.

中文翻译：

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胶质母细胞瘤治疗：基于间充质干细胞的载体携带重组病毒的基本原理。

逃避生长抑制是癌症的显着标志之一。磷酸酶和张力蛋白同源物 (PTEN) 和 p53 肿瘤抑制途径在大多数人类癌症中受到损害，包括胶质母细胞瘤 (GB)。因此，这些信号通路是新型癌症治疗的理想焦点。重组病毒可以选择性地杀死癌细胞并将治疗基因携带到肿瘤中。具体而言，溶瘤病毒 (OV) 已成功用于 GB 动物模型中的基因传递，并显示出中和肿瘤部位免疫抑制的潜力。然而，相关的全身免疫原性、GB 细胞的低效转导以及转移性肿瘤的分布不充分一直是临床研究的主要瓶颈。间充质干细胞 (MSCs)，具有肿瘤嗜性和免疫特权，可以提高 OV 的定位。值得注意的是，将这两种方法结合起来可以解决它们各自的问题。在此，我们总结了一些发现，提倡在 GB 治疗中重新激活肿瘤抑制因子 p53 和 PTEN，并使用 MSC 作为“特洛伊木马”将溶瘤病毒货物运送到播散的肿瘤床。MSCs 和 OVs 的整合可以成为癌症治疗的新范式。