Metastasis accounts for the majority of cancer-related deaths. Despite decades of research, the prevention and suppression of metastasis remain an elusive goal, and to date, only a few metastasis-related genes have been targeted therapeutically. Thus, there is a strong need to find potential genes involved in key driver traits of metastasis and their available drugs. In this study, we identified genes associated with metastasis and repurposable drugs that potentially target them. First, we use text mining of PubMed citations to identify candidate genes associated with metastatic processes, such as invadopodia, motility, movement, metastasis, invasion, wound healing, EMT (epithelial to mesenchymal transition), and podosome. Next, we annotated the top genes involved in each process as a driver, tumor suppressor, or oncogene. Then, a total of 185 unique cancer genes involved in metastasis-related processes were used for hub gene analysis using bioinformatics tools. Notably, a total of 77 hub genes were identified. Further, we used virtual screening data of druggable candidate hub genes involved in metastasis and identified potential drugs that can be repurposed as anti-metastatic drugs. Remarkably, we found a total of 50 approved drugs that have the potential to be repurposed against 19 hub genes involved in metastasis-related processes. These 50 drugs were also found to be validated in different cancer cell lines, such as dasatinib, captopril, leflunomide, and dextromethorphan targeting SRC, MMP2, PTK2B, and RAC1 hub genes, respectively. These repurposed drugs potentially target metastasis, provide pharmacodynamic insight, and offer a window of opportunity for the development of much-needed antimetastatic drugs.
Bibliographical noteFunding Information:
This work was funded by the Israel Cancer Research Fund (grant number 20-101-PG), the Israel Cancer Association (grant number 20210071), and the Israel Science Foundation (grant number2142/21) (to H.G.-H.), as well as the Ginsberg Foundation (to A.O.S.) and the Katz foundation (to A.O.S.).
Funding: This work was funded by the Israel Cancer Research Fund (grant number 20-101-PG), the Israel Cancer Association (grant number 20210071), and the Israel Science Foundation (grant number2142/21) (to H.G.-H.), as well as the Ginsberg Foundation (to A.O.S.) and the Katz foundation (to A.O.S.).
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
- cancer metastasis
- drug repurposing
- hub genes