Current approach in the treatment of hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is the most common malignant hepatobiliary disease; it is responsible for about 1 million deaths per year. Risk factors include hepatitis B and C, hepatic cirrhosis, including alcohol related hepatitis, metabolic and nutritional hepatic damage. The main modality of diffusion is intrahepatic in the natural course of the disease. There are two leading types of treatment: local and systemic. Surgical resection and liver transplantation constitute the most appropriate local treatments and are considered the only real possibility for recovery. Other local approaches include: radiofrequency ablation, percutaneous ethanol ablation, hepatic endoarterial chemoembolization and intrahepatic radiotherapy (SIRT: selective internal radiation therapy). These last treatments are used to control the disease when surgery or transplantation is not achievable; in some cases they are able to prolong survival while they constitute mainly a palliative treatment. Systemic treatments include: chemotherapy, immunological and hormonal therapies and, more recently, the introduction of new specific molecular target drugs. At the moment, in this group, the only drug that has given positive results during phase III trials (SHARP study) is Sorafenib. Sorafenib represents the only primary systemic therapy that has demonstrated, unlike the other treatments previously described, an increase in survival rate in patients affected with advanced HCC. Currently, other studies are taking place that are further developing the potential of this drug. These studies, including phase III trials, are directed in order to test the activity and safety of new emerging drugs with targeted activity. Examples of these new agents are: Sunitinib, Gefitinib, Cetuximab, Bevacizumab and Erlotinib.

Prevalence of K-Ras mutations in hepatocellular carcinoma: A Turkish Oncology Group pilot study

“…Cetuximab has also been used in the treatment of advanced HCC patients, with promising although conflicting results. As it has been suggested by several studies on the role of K-Ras mutations in the prediction of response to cetuximab in colon cancer, it is possible that the K-Ras mutation status may also predict the response to cetuximab in HCC patients (2,3,5,6,15).…”

“…Furthermore, the late detection of HCC is a factor contributing to the poor outcome of HCC patients, as over two-thirds of patients are diagnosed at advanced stages of the disease. However, in the subpopulation of patients who are diagnosed at an early disease stage and who receive potentially curative treatment, such as liver transplantation, surgical resection and tumor ablation, a 5-year survival rate of 40-70% may be expected (1)(2)(3)(4)(5)(6).…”

“…Over the last 4 decades, the incidence of HCC has been on the increase in the developed world. For example, in the United States, the incidence has doubled since the 1970s and the mortality rate from HCC has increased by 41% over this time period (1)(2)(3)(4)(5)(6).…”

The VEGF Pathway in Cancer and Disease: Responses, Resistance, and the Path Forward

“…Sorafenib received FDA approval for advanced/ metastatic RCC based on phase III data showing (Escudier et al 2007). It has also received approval for hepatocellular carcinoma (Rossi et al 2010). Similarly, sunitinib received FDA approval in early 2006 for imatinib-resistant gastrointestinal stromal tumors (GIST) and for metastatic renal cell carcinoma (RCC), showing improved progression-free survival for sunitinib versus IFN-a (11 vs. 5 mo), as well as objective response rate (31% vs. 6%) (Motzer et al 2007).…”

Suppression of the Wnt signaling pathway may contribute to the inhibition of proliferation of human hepatocellular carcinoma SMMC-7721 cells by esculetin

“…Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, with a mortality rate of ~1 million people per year worldwide (1)(2)(3)(4). However, the precise molecular mechanism of HCC tumorigenesis remains largely unknown.…”