Vinorelbine's anti-tumor actions may depend on the mitotic apoptosis, autophagy and inflammation: hypotheses with implications for chemo-immunotherapy of advanced cancers and pediatric gliomas

Journal of Chemotherapy
Meric A AltinozIlhan Elmaci

Abstract

Vinorelbine is a very potent chemotherapeutic agent which is used to treat a number of cancers including breast and non-small cell lung tumors. Vinorelbine mainly acts via blocking microtubules and induces a specific type of cell death called 'mitotic catastrophe/apoptosis' subsequent to mitotic slippage, which is the failure of cells to stay in a mitotic arrested state and replicating their DNA without cytokinesis. Glial tumor cells are especially sensitive to mitotic slippage. In recent years, vinorelbine demonstrated potency in pediatric optic and pontine gliomas. In this manuscript, we propose that vinorelbine's anti-tumor actions involve mitotic apoptosis, autophagy and inflammation. Intravenous infusion of vinorelbine induces a peculiar severe pain in the tumor site and patients with highly vascularized, oedematous and necrotic tumors are particularly vulnerable to this pain. Severe pain is a sign of robust inflammation and anti-inflammatory agents are used in treatment of this side effect. However, no one has questioned whether inflammation contributes to anti-tumor effects of vinorelbine, despite the existing data that vinorelbine induces Toll-Like Receptor-4 (TLR4), cytokines and cell death in endothelial cells especia...Continue Reading

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