Interphase microtubules: chief casualties in the war on cancer?

Abstract

Microtubule-targeting agents (MTAs) profoundly affect interphase cells, such as by disrupting axonal transport, transcription, translation, mitochondrial permeability, immune cell function, directional migration and centrosome clustering. This finding is antithetical to the conventionally held notion that MTAs act on mitosis to trigger arrest-mediated apoptotic cell death. Furthermore, the paucity of mitotic cells in patient tumors and lack of correlation of MTA efficacy with tumor proliferation rate provide strong impetus to re-examine the mechanistic basis of action of MTAs, with an eye toward interphase activities. Whereas targeted antimitotics have unequivocally failed their promise across clinical studies, MTAs constitute a mainstay of chemotherapy. This paradox necessitates the conclusion that MTAs exert mitosis-independent effects, spurring a dramatic paradigm shift in our understanding of the mode of action of MTAs.