Oncogenes: The Passport for Viral Oncolysis Through PKR Inhibition.

Oncogenes: The Passport for Viral Oncolysis Through PKR Inhibition.
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DOI:
10.4137/bic.s33378
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发表时间:
2016
期刊:
Biomarkers in cancer
影响因子:
--
通讯作者:
Fernandes J
Fernandes J
中科院分区:
其他
文献类型:
--
作者:
Fernandes J

文献摘要

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The transforming properties of oncogenes are derived from gain-of-function mutations, shifting cell signaling from highly regulated homeostatic to an uncontrolled oncogenic state, with the contribution of the inactivating mutations in tumor suppressor genes P53 and RB, leading to tumor resistance to conventional and target-directed therapy. On the other hand, this scenario fulfills two requirements for oncolytic virus infection in tumor cells: inactivation of tumor suppressors and presence of oncoproteins, also the requirements to engage malignancy. Several of these oncogenes have a negative impact on the main interferon antiviral defense, the double-stranded RNA-activated protein kinase (PKR), which helps viruses to spontaneously target tumor cells instead of normal cells. This review is focused on the negative impact of overexpression of oncogenes on conventional and targeted therapy and their positive impact on viral oncolysis due to their ability to inhibit PKR-induced translation blockage, allowing virion release and cell death.