Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. The incidence of this disease is increasing and it is one of the key indications for liver transplantation. Chronic infection with hepatitis B virus is the leading cause of HCC, closely followed by infection with hepatitis C virus. Other factors contributing to the development of HCC include alcoholism and obesity. Although treatment options have improved in the past 30 years, particularly with the approval of several molecular-targeted therapies, prognosis remains dismal for many patients. Advances are being made in understanding the mechanisms underlying HCC, which in turn could lead to novel therapeutics, but more progress is urgently needed in this area.
This special Web Collection from Nature Reviews Clinical Oncology and Nature Reviews Gastroenterology & Hepatology comprises a selection of articles covering key aspects of the pathogenesis and treatment of HCC, including insights into disease pathways and possible future therapeutic targets.
This collection has been produced with educational support from Onyx Pharmaceuticals, Inc and Bayer Healthcare LLC, and is freely available for 6 months. All content has been chosen by the editors of Nature Reviews Clinical Oncology and Nature Reviews Gastroenterology & Hepatology.
REVIEWS
Chemopreventive strategies in hepatocellular carcinoma
Siddharth Singh, Preet Paul Singh, Lewis R. Roberts & William Sanchez
doi:10.1038/nrgastro.2013.143
Nature Reviews Gastroenterology & Hepatology, advance online publication, Published online 13 August 2013
In light of the high mortality rate associated with hepatocellular carcinoma (HCC), chemopreventive strategies to prevent or delay the development of this disease are attractive. This Review outlines advances in the field of HCC chemoprevention, in particular focusing on the potential of antiviral therapy against HBV and HCV, the cancer-modifying effects of statins, antidiabetic medications and aspirin, as well as dietary strategies.
Medical therapies for hepatocellular carcinoma: a critical view of the evidence
Augusto Villanueva, Virginia Hernandez-Gea & Josep M. Llovet
doi:10.1038/nrgastro.2012.199
Nature Reviews Gastroenterology & Hepatology 10, 34-42 (2013)
As the burden of hepatocellular carcinoma (HCC) continues to increase, attention turns to the appropriate management of the disease. In this Review, the authors discuss and critique the currently available medical interventions for the treatment and management of HCC, as well as introduce future developments in the field.
Hepatic stem cells and transforming growth factor β in hepatocellular carcinoma
Avijit Majumdar, Steven A. Curley, Xifeng Wu, Powel Brown, Jessica P. Hwang, Kirti Shetty, Zhi-Xing Yao, Aiwu Ruth He, Shulin Li, Lior Katz, Patrizia Farci & Lopa Mishra
doi:10.1038/nrgastro.2012.114
Nature Reviews Gastroenterology & Hepatology 9, 530-538 (2012)
Hepatocellular carcinoma (HCC) is the fifth most commonly occurring cancer and the third most common cause of cancer-related deaths, and the incidence of this cancer is increasing. A substantial portion of HCCs are thought to arise from hepatic stem cells. In this Review, Lopa Mishra and colleagues describe TGF-β signalling in liver stem cell niches, and examine the roles of this cytokine including those in tumour progression and suppression. Important translational studies that are needed to develop novel therapies are discussed.
Hepatocellular carcinoma: insight from animal models
Yan Li, Zhao-You Tang & Jin-Xuan Hou
doi:10.1038/nrgastro.2011.196
Nature Reviews Gastroenterology & Hepatology 9, 32-43 (2012)
Hepatocellular carcinoma (HCC) is the third most common cause of death from cancer worldwide. In this Review Yan Li, Zhao-You Tang and Jin-Xuan Hou provide an overview of animal models that are relevant to HCC development, metastasis and treatment. Viral hepatitis is the single most important cause of HCC and the authors describe transgenic mouse models of HBV and HCV infection that have provided experimental evidence that viral genes could initiate or promote liver carcinogenesis. The criteria for establishing ideal HCC animal models are also discussed.
Reactivation of hepatitis B virus and hepatitis C virus in patients with cancer
Harrys A. Torres & Marta Davila
doi:10.1038/nrclinonc.2012.1
Nature Reviews Clinical Oncology 9, 156-166 (2012)
Patients with cancer who also have hepatitis B virus (HBV) or hepatitis C virus (HCV) infection have a significant morbidity and mortality. HBV reactivation is a serious but preventable complication of immunosuppressive therapy. The authors discuss the epidemiology, pathogenesis, risk factors, and clinical and laboratory manifestations associated with the reactivation of HBV and HCV during immunosuppressive therapy, and discuss strategies for the prevention and treatment of viral reactivation.
HCC and angiogenesis: possible targets and future directions
Andrew X. Zhu, Dan G. Duda, Dushyant V. Sahani & Rakesh K. Jain
doi:10.1038/nrclinonc.2011.30
Nature Reviews Clinical Oncology 8, 292-301 (2011)
Hepatocellular carcinoma (HCC) is notoriously resistant to systemic therapies. The success of the anti-VEGF therapy sorafenib in patients with advanced-stage HCC raises hope as well as critical questions on the future development of targeted agents including other antiangiogenic drugs.
Excess body weight and obesity—the link with gastrointestinal and hepatobiliary cancer
Prashant Kant & Mark A. Hull
doi:10.1038/nrgastro.2011.23
Nature Reviews Gastroenterology & Hepatology 8, 224-238 (2011)
Prashant Kant and Mark Hull discuss the association between excess body weight and cancer risk in the gastrointestinal and hepatobiliary tract. Current understanding of the pathophysiological mechanisms is summarized, as well as the impact that weight loss has on future cancer risk. Finally, the authors describe the relationship between excess body weight and gastrointestinal cancer outcomes.
NF-κB in the liver—linking injury, fibrosis and hepatocellular carcinoma
Tom Luedde & Robert F. Schwabe
doi:10.1038/nrgastro.2010.213
Nature Reviews Gastroenterology & Hepatology 8, 108-118 (2011)
Hepatic cirrhosis and hepatocellular carcinoma (HCC) are the most common causes of death in patients with chronic liver disease. This Review discusses the contribution of NF-κB to chronic liver disease, with a particular focus on the role of NF-κB in different hepatic cell compartments and its effects on chronic inflammation and fibrosis as events that set the stage for the development of HCC.
PERSPECTIVES
Hepatocellular carcinoma—resection or transplant?
Sheung Tat Fan
doi:10.1038/nrgastro.2012.158
Nature Reviews Gastroenterology & Hepatology 9, 732-737 (2012)
Hepatocellular carcinoma (HCC) is the fifth most common malignancy in the world, yet consensus is lacking on whether to treat patients with resection or transplantation. In this Perspectives, Sheung Tat Fan discusses the treatment outcome of HCC by transplantation or resection and the future development of surgical treatment of HCC.
Intra-arterial brachytherapy of hepatic malignancies: watch the flow
Bruno Morgan, Andrew S. Kennedy, Val Lewington, Bleddyn Jones & Ricky A. Sharma
doi:10.1038/nrclinonc.2010.153
Nature Reviews Clinical Oncology 8, 115-120 (2011)
Radio-embolization using radioactive microspheres allows the delivery of high-dose internal radiotherapy to malignant tumors of the liver. The surrogate for measuring flow dynamics for radio-embolization planning does not best represent treatment efficacy. Therefore, Morgan et al. propose that imaging protocols sensitive to changes in vasculature are likely to represent useful predictive markers of malignant lesions that could benefit from radio-embolization.
NEWS & VIEWS
Diagnosis: Novel prognostic biomarkers in hepatocellular carcinoma
Roberta W. C. Pang & Ronnie T. P. Poon
doi:10.1038/nrgastro.2012.208
Nature Reviews Gastroenterology & Hepatology 9, 691-692 (2012)
Liver transplantation: A simple inflammation marker predicts liver cancer prognosis
Zhao-You Tang
doi:10.1038/nrgastro.2011.105
Nature Reviews Gastroenterology & Hepatology 8, 367-368 (2011)
YEAR IN REVIEW
Liver transplantation in 2012: Transplantation for liver cancer—more with better results
Chung-Mau Lo
doi:10.1038/nrgastro.2012.257
Nature Reviews Gastroenterology & Hepatology 10, 74-76 (2013)
Hepatocellular carcinoma in 2011: Genomics in hepatocellular carcinoma—a big step forward
Ryosuke Tateishi & Masao Omata
doi:10.1038/nrgastro.2011.255
Nature Reviews Gastroenterology & Hepatology 9, 69-70 (2012)
RESEARCH HIGHLIGHTS
Gut microbiota: Obesity-induced microbial metabolite promotes HCC
Katrina Ray
doi:10.1038/nrgastro.2013.121
Nature Reviews Gastroenterology & Hepatology 10, 442 (2013)
Cancer: Importance of oncofetal gene, SALL4, in a subset of hepatocellular carcinoma
Isobel Leake
doi:10.1038/nrgastro.2013.115
Nature Reviews Gastroenterology & Hepatology 10, 441 (2013)
Hepatocellular carcinoma: Actopaxin has a role in HCC metastasis
Isobel Leake
doi:10.1038/nrgastro.2013.58
Nature Reviews Gastroenterology & Hepatology 10, 260 (2013)
Liver cancer: The promise of new approaches in the management of hepatocellular carcinoma—adding to the toolbox?
Katrina Ray
doi:10.1038/nrgastro.2013.52
Nature Reviews Gastroenterology & Hepatology 10, 195 (2013)
Immunotherapy: Oncolytic vaccinia virus shows promise in liver cancer
Vanessa Marchesi
doi:10.1038/nrclinonc.2013.31
Nature Reviews Clinical Oncology 10, 182 (2013)
Targeted therapies: Has HCC MET its match?
Rebecca Kirk
doi:10.1038/nrclinonc.2012.220
Nature Reviews Clinical Oncology 10, 3 (2013)
Hepatocellular carcinoma: Could antiplatelet drugs be used to prevent HBV-associated hepatocellular carcinoma?
Claire Greenhill
doi:10.1038/nrgastro.2012.139
Nature Reviews Gastroenterology & Hepatology 9, 425 (2012)
Cancer: Mdm2-regulated stabilization of HuR by neddylation in HCC and colon cancer—a possible target for therapy
Andy McLarnon
doi:10.1038/nrgastro.2011.241
Nature Reviews Gastroenterology & Hepatology 9, 4 (2012)
Treatment modalities: HIFU is effective for unresectable HCC
Lisa Hutchinson
doi:10.1038/nrclinonc.2011.81
Nature Reviews Clinical Oncology 8, 385 (2011)
Hepatocellular carcinoma: Vitamin K2 does not prevent cancer recurrence
Iley Ozerlat
doi:10.1038/nrgastro.2011.101
Nature Reviews Gastroenterology & Hepatology 8, 358 (2011)
Targeted therapies: Doxorubicin and sorafenib improves survival in patients with advanced hepatocellular carcinoma
Lisa Hutchinson
doi:10.1038/nrclinonc.2010.208
Nature Reviews Clinical Oncology 8, 61 (2011)
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