Comprehensive Review on Hepatocellular Carcinoma

About author:
Ramesh Dhani
JNTUA – OTRI, India
E-mail: dhanipharmachem@gmail.com

HCC (hepatocellular carcinoma) prognosis remains dismal despite many treatment options. Overall, the cure rate among patients who undergo resection is not very high and for those patients who are not eligible for surgery or percutaneous procedures, only chemoembolization appears to improve survival…Sorafenib, the only drug approved by the United States Food and Drug Administration for the treatment of advanced HCC, increases the median survival time by less than 3mo. However, this drug does not defer the symptomatic progression of the disease, costs about $5400 per month for treatment, and exhibits severe adverse effects, including a significant risk of bleeding. These drawbacks necessitate the search for novel preventive and therapeutic approaches for this disease.
Hepatocellular carcinoma (HCC) is the most common form of primary hepatic carcinoma and a pressing sociomedical problem in several countries, particularly in Asia and sub-Saharan Africa. HCC is currently the fifth most common cancer and third leading cause of cancer-related deaths in the world. HCC has a poor prognosis with the number of deaths almost equal to the number of cases being diagnosed annually (about 600 000) and the 5-year survival rate is below 9% . In the United States, the incidence of HCC has been steadily rising with a 70% increase registered in the last 25 years. The American Cancer Society, estimated that in 2010 alone, more than 24 000 new cases and nearly 19 000 deaths occurred in the United States due to liver cancer (including biliary cancers).
Major risk factors for HCC are well known and are dependent on the geographic area. In Europe, the United States, and Japan, the main risk factors are liver cirrhosis, Hepatitis B virus (HBV) and Hepatitis C virus (HCV), alcohol, and tobacco; in contrast, in Africa and Asia, the etiological factors include HBV and HCV, tobacco use, and aflatoxin exposure. Treatment for HCC has been conventionally divided into curative and palliative. Curative treatments, such as resection, liver transplantation and percutaneous ablation, induce complete responses in a high proportion of patients and are expected to improve survival. Palliative treatments are not aimed to cure, but in some cases can obtain good response rates and even improve survival. In the west, curative treatments are applied to 30%-40% of patients in referral centers, whereas in Japan 60%-90% of patients benefit because of widespread implementation of surveillance and a broad application of treatments. There is no firm evidence to establish the optimum first-line treatment for patients who have a single small HCC and well-preserved liver function. Resection and transplantation achieve the best outcomes in well-selected candidates (5-year survival 60%-70%), and compete as the first option from an intention-to-treat perspective. Percutaneous treatments provide good results (5-year survival 40%-50%), but have not been able to achieve response rates and outcomes comparable to surgical treatments. Liver transplantation has been suggested as the best treatment for patients with one tumor and decompensated cirrhosis or multicentric small tumors.
HCC prognosis remains dismal despite many treatment options. Overall, the cure rate among patients who undergo resection is not very high and for those patients who are not eligible for surgery or percutaneous procedures, only chemoembolization appears to improve survival. The need thus arises to test novel agents in large-scale randomized trials; these include intraarterial injection of radiolabeled microsphere and new systemic drugs, such as tyrosine kinase inhibitors, antivascular endothelial growth factor (VEGF) antibody, and antiepithelial growth factor recepto. HCC is also widely considered to be a chemotherapy-resistant disease. Sorafenib, the only drug approved by the United States Food and Drug Administration for the treatment of advanced HCC, increases the median survival time by less than 3mo. However, this drug does not defer the symptomatic progression of the disease, costs about $5400 per month for treatment, and exhibits severe adverse effects, including a significant risk of bleeding. These drawbacks necessitate the search for novel preventive and therapeutic approaches for this disease. Chemoprevention has emerged as an ideal approach whereby the occurrence and progression of the disease can be prevented, slowed, or reversed by the administration of one or more naturally occurring and/or synthetic compounds.
Phytochemicals, including those obtained from fruits, vegetables, nuts and spices, have drawn a considerable amount of attention due to their ability to selectively kill tumor cells and suppress carcinogenesis in preclinical animal models. A large number of these plant-derived substances have been shown to significantly prevent or delay cancer development in several high risk populations. Mounting evidence, based on in vitro experiments and studies involving animal models as well as humans, support potential chemopreventive and therapeutic effects of diverse phytochemicals in liver cancer. This review delves into the current use of terpenoids, the largest families of plant-derived natural products, for either chemoprevention or therapy of hepatic cancer, by examining an extensive number of studies conducted both in vitro and in vivo.