*2.2. Oncogene-Induced Perturbations to Antiviral Responses: A Reduction in Impediments to Viral Replication*

Oncogene-induced perturbations to antiviral responses are prominent molecular mechanisms by which the cancer-cell milieu becomes optimized towards OV replication. To exemplify this concept, we focus on such effects related to oncogenic RAS. Oncogenic

mutations in RAS, a GTP-activated molecular switch, ensue exposure to genotoxic agents, and are estimated to occur in 16–30% of all human cancers, with highest incidence in pancreatic (90%) and colon (50%) cancers; and considerable portions of melanoma and lung adenocarcinoma [9–11]. Activated RAS (either because of oncogenic mutations or following stimulation of upstream growth receptors) stimulates downstream signaling pathways mediated by phosphatidylinositol 3 (OH)-kinase (PI3K), RAL guanine nucleotide dissociation stimulator (RALGDS) family members, and members of the RAF family, which activate the RAF/MEK/ERK pathway [12]. Thus, RAS functions as a multi-pronged signaling node, which upon activation, endows tumor cells with multiple malignancyassociated features. Multiple lines of evidence place RAS, and its associated signaling pathways, as negative regulators cell autonomous immunity.
