Vinorelbine in Cancer Therapy

Anna      Capasso

Abstract

Vinorelbine is an antimitotic anticancer agent and its main mechanism of action is related to the inhibition of microtubule dynamics leading to a mitotic arrest and cell death. Vinorelbine, as a microtubule destabilizing agent, stimulates microtubule depolymerization and mitotic spindle destruction at high concentration whereas at lower concentrations, it is able to block mitotic progression. Its main targets are tubulin and microtubules. Vinorelbine binds to β-tubulin subunits at Vinca-binding domain near the positive end of microtubules. The rapid and reversible binding by Vinorelbine to soluble tubulin induces a conformational change that increases the affinity of tubulin for itself which plays a key role in the kinetics of microtubule stabilization. This binding significantly reduces the rate of microtubule dynamics (lengthening and shortening) and increases the duration which microtubules spend in an attenuated state. This helps in proper assembly of the mitotic spindle and hence reduces the tension at the kinetochores of the chromosomes. Subsequently, chromosomes at the spindle poles are unable to progress to the spindle equator. The aim of this review is to examine the mechanism of the inhibition of cell proliferation by Vinorelbine and its efficacy in breast cancer patients in phase II studies.

Keywords: Antimitotic, cancer, vinorelbine, microtubule dynamics leading, tubulin, Vinca-binding, mitotic spindle, chromosomes, cytotoxic drugs, tissue homeostasis