Interfering with mitosis in cancer cells leads to mitotic arrest and, very often, to cell death. This explains the proven success of the antimicrotubule drugs like paclitaxel in the treatment of many cancers. However, their clinical efficacy has been impaired by side effects and drug resistance, highlighting the need of search for new anticancer agents. Our research group is committed to discover mitotic components that could act as potential cancer therapeutic targets. In this context, as the protein p31comet is required for the completion of mitosis, its targeting is expected to affect tumor cell division. Thus, the present proposal has three goals: i) to test the antimitotic activity of p31comet inhibition human cancer, using as model non–small cell lung carcinoma (NSCLC) lines; ii) to determine if p31comet inhibition sensitizes NSCLC cells to paclitaxel in a combination therapy; and iii) to elucidate the mechanistic by which p31comet inhibition induces cancer cell death. It is expected that these results will be the basis of future in vivo experiments using functionalized p31comet-siRNA-loaded nanoparticles, in the context of a 4-year PhD fellowship recently approved by FCT.