Ras-activated defective antiviral signaling pathway (Ras/IFN-deficiency)

The Ras-activated defective antiviral signaling pathway refers to a cellular phenotype where oncogenic signaling, particularly through the Ras/MAPK pathway, suppresses the cell's innate ability to resist viral infection [1]. In normal cells, the presence of viral double-stranded RNA activates the enzyme Protein Kinase R (PKR), which halts protein synthesis and prevents viral spread; however, in many tumor cells, active Ras signaling inhibits PKR activation, rendering the cells susceptible to viral exploitation [1, 3]. Additionally, many cancers acquire defects in the Type I Interferon (IFN) signaling pathway to evade immune detection, further compromising their antiviral defenses [2]. This specific vulnerability is the biological basis for oncolytic virotherapy, where viruses like Reovirus (Pelareorep) are used to selectively infect and lyse tumor cells while sparing healthy, antiviral-competent cells [1, 4]. Consequently, this pathway serves as a functional target for a class of biological therapeutics designed to exploit the inherent signaling imbalances of malignant cells. Understanding this pathway is crucial for identifying patient populations, such as those with KRAS mutations, who may benefit most from oncolytic viral treatments [2, 3]. Sources: [1] Coffey MC, et al. (1998) Science; [2] Stojdl DF, et al. (2000) Cancer Research; [3] Shmulevitz M, et al. (2005) Journal of Virology; [4] Barber GN. (2001) Cell Death & Differentiation.

Other names

Ras-mediated PKR inhibitionDefective Type I Interferon signaling in cancerOncolytic virus susceptibility phenotypeRas-transformed cell antiviral defectImpaired innate antiviral immunity in tumor cells

Selective viral replication and oncolysis in cells with impaired PKR activation or defective Type I Interferon signaling mediated by oncogenic Ras signaling.