Hepatocellular carcinoma treatment over sorafenib: epigenetics, microRNAs and microenvironment. Is there a light at the end of the tunnel?

INTRODUCTION: Sorafenib is currently the only approved therapy in hepatocellular carcinoma (HCC). Alternative first- and second-line treatments are a significant unmet medical need, and several biologic agents have been tested in recent years, with poor results. Therefore, angiogenic pathways and the cytokine cascade remain possible targets in HCC. Recent studies suggest a role of epigenetic processes, associated with the initiation and development of HCC. In this field, DNA methylation, micro-RNAs (miRNAs) and tumor microenvironment cells became a possible new target for HCC treatment. AREAS COVERED: This review explains the possible role of DNA methylation and histone deacetylase inhibitors as predictive biomarkers and target therapy, the extensive world of the promising miRNA blockade strategy, and the recent strong evidence of correlation between HCC tumors and peritumoral stroma cells. The literature and preclinic/clinic data were obtained through an electronic search. EXPERT OPINION: Future research should aim to understand how best to identify patient groups that would benefit most from the prescribed therapy. To overcome the 'therapeutic stranding' of HCC, a possible way out from the current therapeutic tunnel might be to evaluate the major epigenetic and genetic processes involved in HCC carcinogenesis, not underestimating the tumor microenvironment and its 'actors' (angiogenesis, immune system, platelets). We are only at the start of a long journey towards the elucidation of HCC molecular pathways as therapeutic targets. Yet, currently this path appears to be the only one to cast some light at the end of the tunnel.

The European accreditation of Istituto Tumori Giovanni Paolo II of Bari.

The National Cancer Institute of Bari (Istituto di Ricovero e Cura a Carattere Scientifico, IRCCS) has been involved since the conception of the project of the Italian Ministry for Health aimed to validate the applicability of the Organisation of European Cancer Institutes (OECI) accreditation and designation (A&D) model to the Network of Italian Cancer Centers, IRCCS, of Alleanza Contro il Cancro. The self-assessment phase of the Institute started in September 2013 and ended in June 2014. All documents and tools were transferred to the OECI A&D Board in June 2014 and a 2-day peer review visit was conducted in October 2014 by an international qualified audit team. The Institute received its final designation and certification in June 2015. The OECI A&D Board, in its final report, came to the conclusion that Istituto Tumori "Giovanni Paolo II" of Bari has a strong research component with some essential elements of comprehensive cancer care still under development; the lack of a system for using outcome data for the strategic management approach to decision-making and missing a regular internal audit system eventually helping further quality improvement were reported as examples of areas with opportunities for improvement. The OECI A&D process represented a great opportunity for the cancer center to benchmark the quality of its performance according to standard parameters in comparison with other international centers and to further develop a participatory group identity. The common goal of accreditation was real and participatory with long-lasting positive effects. We agree with the OECI comments about the next areas of work in which the Institute could produce future further efforts: the use of its powerful IT system as a means for outcome analysis and empowerment projects for its cancer patients.