Primary liver cancers constitute the fourth most deadly group of cancers.Their poor prognosis is due in part to the pre-existence and/or development,often during treatment,of powerful mechanisms accounting for the poo...Primary liver cancers constitute the fourth most deadly group of cancers.Their poor prognosis is due in part to the pre-existence and/or development,often during treatment,of powerful mechanisms accounting for the poor response of cancer cells to antitumor drugs.These include both impaired gene expression and the appearance of spliced variants,polymorphisms and mutations,affecting the function of genes leading to the reduction in intracellular concentrations of active agents,changes in molecular targets and survival pathways,altered tumor microenvironment and phenotypic transition.The present review summarizes available information regarding the role of germline and somatic mutations affecting drug transporters,enzymes involved in drug metabolism,organelles and signaling molecules related to liver cancer chemoresistance.A more complete picture of the actual complexity of this problem is urgently needed for carrying out further pharmacogenomic studies aimed to improve the management of patients suffering from hepatocellular carcinoma or cholangiocarcinoma.展开更多
基金This study was supported by the Biomedical Research Networking Center in Hepatic and Digestive Diseases-CIBERehd(EHD15PI05/2016)the Health Research Fund,Institute of Health Carlos III,Spain(PI16/00598,co-funded by the European Regional Development Fund/European Social Fund,"Investing in your future")+4 种基金the Spanish Ministry of Economy,Industry and Competitiveness(SAF2016-75197-R)the Regional Government of Castile and Leon(SA063P17)and the AECC Scientific Foundation(2017/2020)Spain.MAP,ASM and PSS were supported by a pre-doctoral contract by“Ministry of Education,Culture and Sports”,Spain(BOE-A-2015-9456 and BOE-B-2017-72875)REE was supported by a pre-doctoral contract funded by the“Junta de Castilla y León,Fondo Social Europeo”(EDU/574/2018).
文摘Primary liver cancers constitute the fourth most deadly group of cancers.Their poor prognosis is due in part to the pre-existence and/or development,often during treatment,of powerful mechanisms accounting for the poor response of cancer cells to antitumor drugs.These include both impaired gene expression and the appearance of spliced variants,polymorphisms and mutations,affecting the function of genes leading to the reduction in intracellular concentrations of active agents,changes in molecular targets and survival pathways,altered tumor microenvironment and phenotypic transition.The present review summarizes available information regarding the role of germline and somatic mutations affecting drug transporters,enzymes involved in drug metabolism,organelles and signaling molecules related to liver cancer chemoresistance.A more complete picture of the actual complexity of this problem is urgently needed for carrying out further pharmacogenomic studies aimed to improve the management of patients suffering from hepatocellular carcinoma or cholangiocarcinoma.
