Molecular bases of the poor response of liver cancer to chemotherapy

A characteristic shared by most frequent types of primary liver cancer, i.e., hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) in adults, and in a lesser extent hepatoblastoma (HB) mainly in children, is their high refractoriness to chemotherapy. This is the result of synergic interactions among complex and diverse mechanisms of chemoresistance (MOC) in which more than 100 genes are involved. Pharmacological treatment, although it can be initially effective, frequently stimulates the expression of MOC genes, which results in the relapse of the tumor, usually with a more aggressive and less chemosensitive phenotype. Identification of the MOC genetic signature accounting for the “resistome” present at each moment of tumor life would prevent the administration of chemotherapeutic regimens without chance of success but still with noxious side effects for the patient. Moreover, a better description of cancer cells strength is required to develop novel strategies based on pharmacological, cellular or gene therapy to overcome liver cancer chemoresistance.