Mitotic inhibitors

Abstract

The cell cycle contains a large number of potential targets for anticancer intervention, and many preclinical models suggest that therapeutic inhibition of such cell cycle associated targets could be beneficial to patients with cancer. Although microtubule-directed therapies have demonstrated clinical activity for over a decade, resistance mechanisms relating to tubulin isoforms have only recently been described. Using this information, epothilones, which seem to be insensitive to tubulin isotype-based mechanisms of resistance, are now being explored to see whether they can demonstrate a convincing advantage over taxanes in such situations. Although the clinical results of cell cycle-related kinase inhibitors are looking promising in hematological malignancies, convincing clinical efficacy in solid tumors, including lung cancer remains elusive. The recent work highlighting the importance of other factors, such as maintenance of mcl-1 levels during cell cycle arrest, that could determine outcomes after mitotic interference may lead to more informative discussions about both predictive biomarkers and rationally designed administration schedules of such inhibitors in the future. Copyright © 2009 by the International Association for the Study of Lung Cancer.