Using Gene-Therapy to Target RAS in Gliomas

An article published in Experimental Biology and Medicine (Volume 246, Issue 10, May, 2021), describes a new treatment strategy for glioma. The study, led by Dr. Julun Yang, in the Department of Pathology at the 920th Hospital of the Joint Logistics Support Force of PLA in Kunming (China), reports that targeting RAS, a gene that promotes tumorigenesis in multiple cancers, enhances antitumor activity against glioma xenografts.
Gliomas are the most common type of central nervous system tumor in humans, with approximately 250,000 cases reported annually worldwide. Current treatment options include aggressive surgical resection, radiation therapy and chemotherapy. Nonetheless, the survival rate for patients is poor, and new treatments are needed. RAS genes play a critical role in regulating cell proliferation, differentiation, migration, apoptosis and senescence. Overexpression of and mutations in RAS genes promote tumorigenesis in numerous types of cancers, including gliomas. Nevertheless, there are no therapies targeting RAS approved for use in patients.
In the current study, Dr. Yang and colleagues used a gene therapy approach to deliver antibodies that inhibit RAS to glioma cells and tumors. Adenovirus delivery of a RAS antibody gene to glioma cells resulted in anti-RAS antibody expression, decreased growth and proliferation, and increased cell death. Intravenous delivery using cytokine-induced killer cells resulted in expression of high levels of RAS antibodies in tumors and low levels in normal organs. Furthermore, tumor volume was reduced and accompanied by decreased cell proliferation and expression of anti-apoptotic genes as well as increased cell death and expression of pro-apoptotic genes. Collectively, these results suggest that gene therapy targeting RAS may be a safe and effective treatment for glioma and other RAS-driven cancers.
Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology & Medicine, said, “Dr. Yang and colleagues have performed in vitro and in vivo studies that provide compelling evidence that the delivery of anti-p21Ras scFv by recombinant adenovirus and cytokine-induced killer cells may be an effective therapy against gliomas and, by extension, other Ras-driven cancers.”
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Source: Experimental Biology and Medicine