Jornal de Carcinogênese e Mutagênese

Abstrato

Why Liver Cancer is so Highly Refractory to Chemotherapy?

Marin JJG

In contrast to important advances in early diagnosis of primary liver cancer, both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), and the curative alternatives available to treat these patients, the pharmacological strategies used in adjuvant chemotherapy and in advanced tumors are poorly effective, whereas similar regimes result in much better outcome in other types of cancer. The reason for the marked refractoriness of liver cancer to antitumor drugs, even the newest inhibitors of receptors with tyrosine kinase activity (TKI), is the participation in the overall multidrug resistance (MDR) phenotype of very different mechanisms that are yet poorly understood. This justifies the effort that is being carried out to obtain a complete picture of the question, which will allow us to identify the precise genetic fingerprint accounting for the MDR phenotype present in each tumor at each moment, from diagnosis to the end of treatment. This information shall be valuable to prevent unnecessary use of pharmacological regimes without expected beneficial effect but with potential noxious consequences. Finally, a better understanding of the molecular bases of the problem is also required to develop novel strategies aimed to fight HCC and CCA chemoresistance.