Crit Rev Oncol Hematol. 2026 Apr 12;223:105337. doi: 10.1016/j.critrevonc.2026.105337. Online ahead of print.
ABSTRACT
Hepatocellular carcinoma (HCC) ranks among the most prevalent and lethal malignancies worldwide. The majority of patients are diagnosed at advanced stages, where current targeted therapies benefit only a subset of patients. Consequently, there is a pressing need to identify novel therapeutic targets and develop corresponding treatment strategies. Human endogenous retroviruses (HERVs), which constitute approximately 8% of the human genome, represent remnants of ancient viral infections and have been increasingly implicated in cancer pathogenesis. In HCC, HERVs exhibit a significant "double-edged sword" characteristic in the occurrence and development of cancer, having both oncogenic and tumor-suppressive effects. On the one hand, the oncogenic mechanisms mainly involve oncogenic lncRNAs derived from HERVs, the formation of virus-like particles, and the regulation of oncogene expression as alternative promoters/enhancers. On the other hand, the tumor-suppressive effects are achieved through mechanisms such as viral mimicry activating antiviral pathways, the production of tumor-suppressive lncRNAs, and the presentation of tumor-specific neoantigens. This review will systematically elucidate the bidirectional regulatory mechanisms of HERVs in liver cancer and explore future research directions in the field of HERV-related liver cancer.
PMID:41974391 | DOI:10.1016/j.critrevonc.2026.105337