Mapping Three Decades of Rho GTPase Signalling in Cancer: Unveiling Loopholes and Future Directions (1990-2024)

Rho GTPases, including RhoA, Rac1, and Cdc42, are central regulators of cytoskeletal dynamics, cell migration, proliferation, and survival, and their dysregulation is firmly implicated in cancer initiation and progression. Although extensive mechanistic and translational studies have been conducted over the past three decades, the overall research landscape linking Rho GTPase signalling to cancer remains dispersed across biological processes, tumour types, and therapeutic strategies. In this study, we performed a bibliometric analysis of 1,457 articles published between 1990 and 2024, retrieved from the Web of Science Core Collection, and refined through manual screening. Quantitative analyses were conducted using Microsoft Excel, and collaboration, co-citation, and keyword networks were visualized using VOSviewer. Our analysis reveals a substantial increase in publications after 2004, with Oncogene identified as a leading journal and the United States as the most prolific contributing country. The literature predominantly focuses on core hallmarks of cancer, including epithelial-mesenchymal transition, tumour invasion, and metastasis, with breast cancer emerging as the most frequently studied disease context. Canonical Rho GTPases, RhoA, Rac1, and Cdc42 dominate the field as key mechanistic drivers and prognostic markers. In contrast, atypical Rho GTPases remain comparatively understudied. Although Rho GTPase signalling has been widely investigated as a therapeutic target, clinical translation remains challenging, largely due to signalling redundancy, pathway plasticity, and tumour adaptive responses rather than insufficient research activity. Collectively, these findings highlight persistent gaps, including limited integration with immuno-oncology and precision medicine frameworks and underexplored roles of non-canonical Rho GTPases. This bibliometric assessment provides a structured overview of three decades of research and identifies priorities to guide future investigations into Rho GTPase-driven cancer biology and therapy.