Hepatocellular Carcinoma: Novel Molecular Targets in Carcinogenesis for Future Therapies

Bertino, Gaetano; Demma, Shirin; Ardiri, Annalisa; Proiti, Maria; Gruttadauria, Salvatore; Toro, Adriana; Malaguarnera, Giulia; Bertino, Nicoletta; Malaguarnera, Michele; Malaguarnera, Mariano; Carlo, Isidoro Di

doi:10.1155/2014/203693

Cited by 62 publications

(64 citation statements)

References 104 publications

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“…Development and progression of HCC is still not a completely known multistage process. Genetic, epigenetic and immunological factors probably contribute to the development of HCC [7,11,13,37,38,50,51,101,297,298] .…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, HBV and HCV co-infection causes a higher than 50-fold risk compared to HCC [51][52][53][54] . Risk factors for liver cancer in HBV patients include:…”

Section: Development Of Hcc In Chronic Hbv Infectionmentioning

confidence: 99%

“…Despite the progress achieved in understanding the cancer process and the impact of this knowledge on treatment, primary prevention remains the most effective approach to reduce cancer mortality in both developed and developing countries for the near future [9,37,38,50,51,56,309] . …”

Section: Future Directionsmentioning

confidence: 99%

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Hepatocellular carcinoma and the risk of occupational exposure

Rapisarda

Loreto

Malaguarnera

et al. 2016

WJH

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Hepatocellular carcinoma (HCC) is the most common type of liver cancer. The main risk factors for HCC are alcoholism, hepatitis B virus, hepatitis C virus, nonalcoholic steatohepatitis, obesity, type 2 diabetes, cirrhosis, aflatoxin, hemochromatosis, Wilson's disease and hemophilia. Occupational exposure to chemicals is another risk factor for HCC. Often the relationship between occupational risk and HCC is unclear and the reports are fragmented and inconsistent. This review aims to summarize the current knowledge regarding the association of infective and non-infective occupational risk exposure and HCC in order to encourage further research and draw attention to this global occupational public health problem. Core tip: Hepatocellular carcinoma (HCC) is the fifth most common human cancer. This review summarizes current knowledge regarding the occupational risk factors of HCC. In particular, we underline not only the infective but also non-infective occupational risk exposure, including chemical agents and toxic metabolites which are a major cause of liver damage.

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Section: Discussionmentioning

confidence: 99%

“…Moreover, HBV and HCV co-infection causes a higher than 50-fold risk compared to HCC [51][52][53][54] . Risk factors for liver cancer in HBV patients include:…”

Section: Development Of Hcc In Chronic Hbv Infectionmentioning

confidence: 99%

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Hepatocellular carcinoma and the risk of occupational exposure

Rapisarda

Loreto

Malaguarnera

et al. 2016

WJH

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“…Several studies have concluded that the eradication of HCV infection slows the progression of the disease, improves the survival, and reduces the incidence of liver failure and the risk of developing liver cancer [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] . The understanding of the natural history of chronic hepatitis C and its long-term consequences is essential to enable appropriate decisions on treatment, but unfortunately the natural history of HCV infection is still the subject of much controversy.…”

Section: Natural History Of Chronic Hepatitis Cmentioning

confidence: 99%

Chronic hepatitis C: This and the new era of treatment

Bertino

Ardiri

Proiti

et al. 2016

WJH

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Over the last years it has started a real revolution in the treatment of chronic hepatitis C. This occurred for the availability of direct-acting antiviral agents that allow to reach sustained virologic response in approximately 90% of cases. In the near future further progress will be achieved with the use of pan-genotypic drugs with high efficacy but without side effects. Core tip: This review analyzes the current therapies for chronic hepatitis C and the future challenges of the research. So it tries to give an update on the research of hepatitis C virus (HCV) infection, providing a critical view of the emerging therapies and their impact on the future management of HCV infection. Since novel TOPIC HIGHLIGHT Chronic hepatitis C: This and the new era of treatment2016 Hepatitis C Virus: Global view treatments for HCV infection are highly efficacious but costly, priority should be given to patients with advanced hepatic fibrosis, which is a disease that cannot be deferred. INTRODUCTIONThe hepatitis C virus (HCV), identified in the 70s but cloned in 1989, is a single-stranded RNA virus belonging to the family Flaviviridae.HCV is the main cause of progressive liver diseases and a public health problem worldwide. It is estimated that approximately 150-180 million people in the world are living with chronic hepatitis [1,2] , 350 million of whom die each year from liver damage associated with the infection [3] . About 80% of people infected with HCV develop chronic hepatitis, of which 20%-40% will develop liver cirrhosis or hepatocellular carcinoma (HCC) 20-30 years after infection.As a consequence, chronic HCV infection is the major reason of liver transplantation in developed countries [4][5][6][7] . According to the Global Burden Disease Study in Europe, the death rate for viral hepatitis is significantly higher than that for human immunodeficiency virus (HIV) and acquired immune deficiency syndrome; in particular in 2010, the number of deaths from viral hepatitis have been ten times bigger than that attributed to HIV. It is reasonable to think that this difference is due to the lack of effective therapies for HCV until a few years ago [8] .HCV is also one of the main causes of death [9] . The virus causes both liver damage and extra-hepatic manifestations, many of these syndromes are associated with the ability of HCV to replicate in peripheral blood mononuclear cells (PBMCs); an example is the mixed cryoglobulinemia, which is by far the most common extrahepatic disease closely connected with the infection.Recently it was shown that antiviral treatment is associated with improved renal and cardiovascular outcomes in patients with cryoglobulinemia [4,6,10,11] . Newly approved oral anti-HCV drugs are very safe and effective, but unfortunately their cost will force to choose a priority of treatment. The intent should therefore be to identify and treat patients with a higher risk of morbidity and mortality due to HCV.The availability of these new oral treatments can definitely heal patients and ...

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“…VEGF levels have been shown to correlate with angiogenic activity, tumor progression, and poor prognosis; its effects are mediated by interactions with the tyrosine kinase receptors VEGFR-1, VEGFR-2, and VEGFR-3 (4).…”

Section: Introductionmentioning

confidence: 99%

Safety and Pharmacokinetics of Lenvatinib in Patients with Advanced Hepatocellular Carcinoma

Ikeda

Okusaka

Mitsunaga

et al. 2016

Clinical Cancer Research

164

139

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Purpose: To determine the maximum tolerable dose (MTD), safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of lenvatinib in patients with advanced hepatocellular carcinoma (HCC).Experimental Design: This multicenter, open-label, phase I, dose-escalation study included patients aged 20 to 80 years, refractory to standard therapy, and stratified by hepatic function measured using Child-Pugh (CP) scores: CP-A (score, 5-6) and CP-B (score, 7-8). Lenvatinib was administered continually once daily for 4-week cycles. MTD was defined as the maximum dose associated with 1 dose-limiting toxicity (DLT) occurring in cycle 1 among 6 patients.Results: In total, 20 patients (9 in CP-A and 11 in CP-B) were enrolled. The MTD was 12 and 8 mg once daily in CP-A and CP-B, respectively; DLTs included proteinuria, hepatic encephalopathy, and hyperbilirubinemia. The most common grade 3 toxicities included hypertension in CP-A and hyperbilirubinemia in CP-B. Lenvatinib plasma concentration at 24 hours after administration (C 24 h ) for 12 mg once daily was higher in patients with HCC than in patients with other solid tumors shown in a previous phase I study, but C 24 h for 25 mg once daily lenvatinib was comparable. After lenvatinib treatment, the number of circulating endothelial and c-Kit þ cells decreased and the levels of interleukin (IL)-6, IL10, granulocyte-colony stimulating factor, and vascular endothelial growth factor increased (P < 0.05). Partial responses were observed in 3 patients and tumor shrinkage occurred in 14 patients. Conclusions: Lenvatinib (12 mg once daily) demonstrated preliminary efficacy with manageable toxicity and is the recommended dose for phase II studies in patients with HCC and CP-A.

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Hepatocellular Carcinoma: Novel Molecular Targets in Carcinogenesis for Future Therapies

Cited by 62 publications

References 104 publications

Hepatocellular carcinoma and the risk of occupational exposure

Hepatocellular carcinoma and the risk of occupational exposure

Chronic hepatitis C: This and the new era of treatment

Safety and Pharmacokinetics of Lenvatinib in Patients with Advanced Hepatocellular Carcinoma

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