Oncogenic potential of SARS-CoV-2—targeting hallmarks of cancer pathways

Abstract

The 2019 outbreak of SARS-CoV-2 has caused a major worldwide health crisis with high rates of morbidity and death. Interestingly, it has also been linked to cancer, which begs the issue of whether it plays a role in carcinogenesis. Recent studies have revealed various mechanisms by which SARS-CoV-2 can influence oncogenic pathways, potentially promoting cancer development. The virus encodes several proteins that alter key signaling pathways associated with cancer hallmarks. Unlike classical oncogenic viruses, which transform cells through viral oncogenes or by activating host oncogenes, SARS-CoV-2 appears to promote tumorigenesis by inhibiting tumor suppressor genes and pathways while activating survival, proliferation, and inflammation-associated signaling cascades. Bioinformatic analyses and experimental studies have identified numerous interactions between SARS-CoV-2 proteins and cellular components involved in cancer-related processes. This review explores the intricate relationship between SARS-CoV-2 infection and cancer, focusing on the regulation of key hallmarks driving initiation, promotion and progression of cancer by viral proteins. By elucidating the underlying mechanisms driving cellular transformation, the potential of SARS-CoV-2 as an oncovirus is highlighted. Comprehending these interplays is essential to enhance our understanding of COVID-19 and cancer biology and further formulating strategies to alleviate SARS-CoV-2 influence on cancer consequences. Graphical Abstract Schematic representation of SARS-CoV-2 associated alterations contributing to various hallmarks of cancer. PI3K/ AKT/mTOR: Phosphoinositide 3-kinase/Protein Kinase B/ Mammalian Target of Rapamycin; TGF-β, Transforming Growth Factor-beta; VEGF, Vascular Endothelial Growth Factor; JNK, Jun N-terminal Kinase; HDAC, Histone Deacetylase; DNMT, DNA Methyltransferase; HIF-1α: Hypoxia-Inducible Factor 1-alpha; pRB, Retinoblastoma Protein. This image was created using BioRender software.