Apoptosis in liver carcinogenesis and chemotherapy

Abstract

Hepatocellular carcinoma (HCC) is a major health problem. In human hepatocarcinogenesis, the balance between cell death and proliferation is deregulated, tipping the scales for a situation where antiapoptotic signals are overpowering the death-triggering stimuli. HCC cells harbor a wide variety of mutations that alter the regulation of apoptosis and hence the response to chemotherapeutical drugs, making them resistant to the proapoptotic signals. Considering all these modifications found in HCC cells, therapeutic approaches need to be carefully studied in order to specifically target the antiapoptotic signals. This review deals with the recent relevant contributions reporting molecular alterations for HCC that lead to a deregulation of apoptosis, as well as the challenge of death-inducing chemotherapeutics in current HCC treatment.

Keywords:

• apoptosis
• death receptors
• HCC
• liver
• sorafenib
• survival signals
• targeted therapy
• TGF-β

Acknowledgements

Certain elements in the figures have been provided by Servier Medical Art (Servier).

Financial & competing interests disclosure

Research in the authors’ group is supported by grants from the Ministry of Economy and Competitiveness (MINECO), Spain (BFU2012-35538 and ISCIII-RTICC: RD12-0036-0029) and People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA grant agreement # PITN-GA-2012-316549 (IT LIVER). The authors are also supported by the European Cooperation in Science and Technology (COST Action BM1203/EU-ROS). J Moreno-Càceres is recipient of a predoctoral contract from the Ministry of Education, Culture and Sport (MEC), Spain (#AP2010-3036). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

Research in the authors’ group is supported by grants from the Ministry of Economy and Competitiveness (MINECO), Spain (BFU2012-35538 and ISCIII-RTICC: RD12-0036-0029) and People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA grant agreement # PITN-GA-2012-316549 (IT LIVER). The authors are also supported by the European Cooperation in Science and Technology (COST Action BM1203/EU-ROS). J Moreno-Càceres is recipient of a predoctoral contract from the Ministry of Education, Culture and Sport (MEC), Spain (#AP2010-3036). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.