Sorafenib, a new generation antitumor drug used in kidney and liver tumors among others, has the ability to block some of the key processes for tumor development and progression, such as proliferation, angiogenesis (formation of new vessels) or the motility of tumor cells. This research has shown how MEK5, an activator of the oncogenic protein ERK5, is a new target of Sorafenib, allowing to explain some antitumor effects of the drug such as blocking the proliferation or migration of tumor cells. Also, this research lays the groundwork for extending its use in other pathologies where ERK5 signalling pathway alterations have been described, as in the case of some types of lung tumors.
This work, core of the doctoral thesis of Marta Ortega Muelas, fellow of the Leticia Castillejo Castillo Foundation, has been directed by Ricardo Sánchez Prieto (Instituto de Investigaciones Biomédicas de Madrid CSIC-UAM), also co-director of the Laboratory of Molecular Oncology of the Centro Regional de Investigaciones Biomédicas (University of Castilla la Mancha, UCLM), together with Dr. Maria José Ruiz Hidalgo, professor of the UCLM. In addition, Dr. José A. Encinar (Universidad Miguel Hernández, Elche) and Dr. Borja Belandia and Dr. Isabel Sánchez Pérez (Instituto de Investigaciones Biomédicas de Madrid CSIC-UAM) have collaborated in this project.
This project has been financed by the Agencia Estatal de Investigación (Spanish Ministry of Science and Innovation) and funds from the Vice-rectorate of Science Policy of the UCLM. Link to the research article: ERK5 signalling pathway is a novel target of sorafenib: Implication in EGF biology - PubMed (nih.gov)
In the figure: detail of the interaction between MEK5 and ERK5. The red arrow indicates the sorafenib binding site in MEK5.