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Molecular Bases of Liver Cancer Refractoriness to Pharmacological Treatment

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Hepatocellular carcinoma and cholangiocarcinoma are the two most important primary malignancies of the liver. These are among the tumours with the lowest response to pharmacological treatment based on currently available drugs. This is due either to the existence of refractoriness of the initial tumour or to the ability of cancer cells to develop chemoresistance during treatment. Liver cancers share some of the mechanisms responsible for drug refractoriness with other types of tumours, such as a reduction in drug uptake; enhanced drug export; intracellular inactivation of the active agent; alteration of the molecular target; an increase in the activity of the target route to be inhibited, or the appearance or stimulation of alternative routes; enhanced repair of drug-induced modifications in the target molecules, and the activation/ inhibition of intracellular signalling pathways, all of which lead to a negative balance between the apoptosis/survival of tumour cells. The aim of the present article is to review how these mechanisms of chemoresistance affect the different families of drugs that are being or have been used to treat hepatocellular carcinoma and cholangiocarcinoma. A better understanding of the molecular bases of drug refractoriness is needed in order to develop novel drugs or pharmacological strategies aimed at overcoming resistance to anticancer agents.

Keywords: ABC proteins; Anticancer Drugs; Apoptosis; Cholangiocarcinoma; Efflux; Hepatocellular Carcinoma; Survival; Uptake

Document Type: Research Article


Affiliations: Department of Physiology and Pharmacology, Campus Miguel de Unamuno E.I.D. S-09, 37007- Salamanca, Spain.

Publication date: March 1, 2010

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.

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