Systemic treatment for hepatocellular carcinoma: Still unmet expectations

Abstract

Many patients with hepatocellular carcinoma (HCC) are diagnosed in an advanced stage, so they cannot be offered the option of curative treatments. The results of systemic chemotherapy are unsatisfactory and this has led to molecular targeted approaches. HCC develops in chronically damaged tissue due to cirrhosis in most patients. Several different cell types and molecules constitute a unique microenvironment in the liver, which has significant implications in tumor development and invasion. This, together with genome instability, contributes to a significant heterogeneity which is further enhanced by the molecular differences of the underlying causes. New classifications based on genetic characteristics of the tissue microenvironment have been proposed and key carcinogenic signaling pathways have been described. Tumor and adjacent tissue profiling seem biologically promising, but have not yet been translated into clinical settings. The encouraging first results with molecular - genetic signatures should be validated and clinically applicable. A more personalized approach to modern management of HCC is urgently needed.

Communicative reprogramming non-curative hepatocellular carcinoma with low-dose metronomic chemotherapy, COX-2 inhibitor and PPAR-gamma agonist: a phase II trial

“…Since 2008 sorafenib became standard treatment of advanced HCC in patients. Recently, lenvatinib proofed to be equivalent efficacious [ 6 ].…”

“…Moreover, the disease control rate of 79% compares with data obtained by classic targeted therapies including brivanib, sunitinib, sorafenib plus erlotinib (phase III trials in first-line), or in second-line brivanib, everolimus, ramucirumab (7.6–9.4 months median OS), or immune checkpoint inhibitors (in phase II) with a disease control rate of about 70% [ 6 , 16 ].…”

“…Sorafenib is a multi-tyrosine kinase inhibitor that targets the vascular endothelial growth factor receptor (VEGF-R), the platelet-derived growth factor receptor (PDGF-R) and the raf-signaling cascade [ 5 ]. Since then multiple targeted therapies have been tested and ongoing phase III trials must still confirm therapeutic improvement [ 6 ].…”

Combined Hyperthermia and Radiation Therapy for Treatment of Hepatocellular Carcinoma

“…Roba M Talaat 1 *, Tamer M Abo-Zeid 1 , Mahmoud T Abo-Elfadl 2 , Eman A El-Maadawy 1 , Mona M Hassanin 3 parenchymal disease (Llovet et al, 2015) Furthermore, the advanced neoplastic stage, severity of liver diseases or shortage lack of donors, restrict their application. For those cases, non-surgical therapies as chemotherapy and radiotherapy are recommended (Samonakis and Kouroumalis, 2017).…”

“…Annually, around 1% of all deaths in the world were related to HCC. Despite recent discoveries in screening strategies and novel therapeutic options, HCC is still the third leading cause of cancer mortality worldwide and remains one of the most difficult tumors to treat (Samonakis and Kouroumalis, 2017).…”