Oncogenic Signaling Induced by HCV Infection
Abstract
The liver is frequently exposed to toxins, metabolites, and oxidative stress, which can challenge organ function and genomic stability. Liver regeneration is therefore a highly regulated process involving several sequential signaling events. It is thus not surprising that individual oncogenic mutations in hepatocytes do not necessarily lead to cancer and that the genetic profiles of hepatocellular carcinomas (HCCs) are highly heterogeneous. Long-term infection with hepatitis C virus (HCV) creates an oncogenic environment by a combination of viral protein expression, persistent liver inflammation, oxidative stress, and chronically deregulated signaling events that cumulate as a tipping point for genetic stability. Although novel direct-acting antivirals (DAA)-based treatments efficiently eradicate HCV, the associated HCC risk cannot be fully eliminated by viral cure in patients with advanced liver disease. This suggests that HCV may persistently deregulate signaling pathways beyond viral cure and thereby continue to perturb cancer-relevant gene function. In this review, we summarize the current knowledge about oncogenic signaling pathways derailed by chronic HCV infection. This will not only help to understand the mechanisms of hepatocarcinogenesis but will also highlight potential chemopreventive strategies to help patients with a high-risk profile of developing HCC.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 02, 2018
- Source ID
- 10.3390/v10100538
Entities
People
- Alessia Virzì
- Armando Roca Suarez
- Joachim Lupberger
- Thomas Baumert
Organizations
- Agence Nationale de la Recherche
- Agence nationale de recherches sur le SIDA
- Association pour le développement de la recherche sur le cancer
- European Research Council
- National Cancer Institute
- National Institute of Allergy and Infectious Diseases
- United States Department of Defense