Modulation of the FAK-Src Signalling Axis by Oncoviruses: Molecular Mechanisms, Functional Consequences, and Therapeutic Opportunities.

Oncoviruses play a role in cellular transformation and cancer progression by manipulating host signalling pathways, such as the FAK-Src axis. Preclinical evidence suggests that viral proteins can modulate this axis through direct interactions, integrin signalling, tumour suppressor inactivation, transcriptional and kinase reprogramming, calcium/ROS signalling, regulation of phosphatases, and epigenetic modifications. Important examples include HPV E2 and E6/E7, EBV LMP1 and LMP2A, HBV HBx, HCV Core and E2, and KSHV proteins. FAK-Src disruption can activate pathways such as PI3K/AKT, Rho GTPase, AP-1, and NF-κB, thereby enhancing migration, invasion, survival, angiogenesis, and modulation of the immune response. In some infections, this axis may also be involved at different stages of the viral life cycle. This review examines the molecular mechanisms of FAK-Src regulation by oncoviruses and its functional and therapeutic implications. It also reviews FAK/Src targeting strategies, distinguishing experimental inhibitors, multitargeted agents, and compounds under clinical evaluation, emphasising the limited clinical evidence specific to each virus. Finally, pFAK and pSrc are reviewed as potential markers of pathway activation and pharmacodynamic interaction with the target; however, current evidence is insufficient for their use as valid diagnostic or predictive biomarkers. A better understanding of the virus-host-FAK/Src interaction could help develop mechanism-based therapeutic approaches and biomarker-based patient selection.