Microtubule-targeting agents in oncology and therapeutic potential in hepatocellular carcinoma
Herbert H Loong, Winnie Yeo
Department of Clinical Oncology, Sir YK Pao Centre for Cancer, Hong Kong Cancer Institute, State Key Laboratory in Oncology in South China, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong
Abstract: In mammalian cells, microtubules are present both in interphase and dividing cells. In the latter, microtubules forming the mitotic spindle are highly dynamic and exquisitely sensitive to therapeutic inhibitors. Developed to alter microtubule function, microtubule-binding agents have been proven to be highly active as an anticancer treatment. Significant development of microtubule-binding agents has taken place in recent years, with newer anti-tubulin agents now showing novel properties of enhanced tumor specificity, reduced neurotoxicity, and insensitivity to chemoresistance mechanisms. Hepatocellular carcinoma remains one of the most difficult cancers to treat, with chemotherapies being relatively ineffective. There is now evidence to suggest that microtubule-binding agents may be effective in the treatment of hepatocellular carcinoma, especially when used in combination with mammalian target of rapamycin inhibitors. Preclinical models have suggested that the latter may be able to overcome resistance to microtubule binding agents. In this review article, recent developments of novel microtubule binding agents and their relevance to the treatment of hepatocellular carcinoma will be discussed.
Keywords: chemotherapy, microtubule-binding agents, microtubular stabilization and destabilization, mTOR inhibition