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Targeted therapy of hepatocellular cancer

Published on Feb 1, 2010in Expert Opinion on Investigational Drugs4.031
· DOI :10.1517/13543780903514110
Piotr J. Wysocki15
Estimated H-index: 15
Abstract
Importance of the field: Hepatocellular cancer (HCC) is the fifth most common malignancy worldwide and third leading cause of cancer death. HCC is highly resistant to conventional systemic therapies, and prognosis for advanced HCC patients remains poor. However, identification of signaling pathways responsible for HCC growth and progression such as RAS/RAF/MEK/ERK or PI3K/AKT/mTOR has determined crucial molecular targets and led to development of novel promising targeted therapies.Areas covered in this review: This article presents molecular mechanisms responsible for development and progression of HCC and strategies aimed to block important molecules involved in signal transduction. It also reviews the clinical studies evaluating efficacy and safety of novel targeted approaches for treatment of this malignancy.What the reader will gain: Inhibition of molecular targets (ligands, membrane receptors and receptor-associated kinases) represents a promising strategy for treatment of HCC; in the case of sorafen...
  • References (109)
  • Citations (44)
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References109
Newest
#1J.-L. RaoulH-Index: 9
#2Richard S. FinnH-Index: 52
Last. Ian WaltersH-Index: 13
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4577 Background: Brivanib is an orally available dual inhibitor of vascular endothelial growth factor and fibroblast growth factor (FGF) signaling. FGF pathway activation is of increasing importance in the setting of liver fibrosis and HCC. This phase II study aimed to assess the efficacy and safety of brivanib in patients (pts) with unresectable, locally advanced or metastatic HCC who had received either no prior systemic therapy (Cohort A) or one prior regimen of angiogenesis inhibitor (Cohort...
63 Citations
#1Zuo-Lin Xiang (Fudan University)H-Index: 7
#2Zhao-Chong Zeng (Fudan University)H-Index: 15
Last. Jian He (Fudan University)H-Index: 8
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Background The chemokine and bone marrow-homing receptor CXCR4 is implicated in metastases of various cancers. This study was conducted to analyze the association of CXCR4 expression with hepatocellular carcinoma (HCC) bone metastasis and patient survival.
57 CitationsSource
#1Shuji OginoH-Index: 85
#2Katsuhiko NoshoH-Index: 53
Last. Charles S. FuchsH-Index: 126
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Purpose Loss of heterozygosity (LOH) at chromosome 18q frequently occurs late during colon cancer development and is inversely associated with microsatellite instability (MSI). 18q LOH has been reported to predict shorter survival in patients with colorectal cancer, whereas MSI-high status has been associated with superior prognosis. However, it is unclear whether 18q LOH in colorectal cancer has any prognostic implication independent of MSI status and other potential predictors of clinical outc...
98 CitationsSource
#1Hung HuynhH-Index: 20
#2K.H. Pierce Chow (SGH: Singapore General Hospital)H-Index: 1
Last. Evelyn TranH-Index: 4
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Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide and highly resistant to available chemotherapies. Mammalian target of rapamycin (mTOR) functions to regulate protein translation, angiogenesis and cell cycle progression in many cancers including HCC. In the present study, subcutaneous patient-derived HCC xenografts were used to study the effects of an mTOR inhibitor, RAD001 (everolimus), on tumour growth, apoptosis and angiogenesis. We report that oral administration o...
105 CitationsSource
#1Andrew X Zhu A X (Partners HealthCare)H-Index: 66
#2Dushyant V. SahaniH-Index: 72
Last. Rakesh K. JainH-Index: 170
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Purpose To assess the safety and efficacy of sunitinib in patients with advanced hepatocellular carcinoma (HCC) and explore biomarkers for sunitinib response. Patients and Methods We conducted a multidisciplinary phase II study of sunitinib, an antivascular endothelial growth factor receptor tyrosine kinase inhibitor, in advanced HCC. Patients received sunitinib 37.5 mg/d for 4 weeks followed by 2 weeks of rest per cycle. The primary end point was progression-free survival (PFS). We used functio...
385 CitationsSource
Background: Hepatocellular carcinoma (HCC) develops most often in a background of chronic inflammatory liver injury from viral infection or alcohol use. Most HCCs are diagnosed at a stage at which surgical resection is not feasible. Even in patients receiving surgery rates of recurrence and metastasis remain high. There are few effective HCC therapies and hence a need for novel, rational approaches to treatment. Platelet derived growth factor receptor-α (PDGFR-α) is involved in tumor angiogenesi...
31 CitationsSource
#1Melanie B. Thomas (University of Texas MD Anderson Cancer Center)H-Index: 22
#2Jeffrey S. MorrisH-Index: 53
Last. James L. Abbruzzese (University of Texas MD Anderson Cancer Center)H-Index: 105
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Purpose The study objective was to determine the proportion of patients with hepatocellular carcinoma (HCC) treated with the combination of bevacizumab (B) and erlotinib (E) who were alive and progression free at 16 weeks (16-week progression-free survival [PFS16]) of continuous therapy. Secondary objectives included response rate, median PFS, survival, and toxicity. Patients and Methods Patients who had advanced HCC that was not amenable to surgical or regional therapies, up to one prior system...
277 CitationsSource
#1Richard S. Finn (UCLA: University of California, Los Angeles)H-Index: 52
#2Greg Bentley (UCLA: University of California, Los Angeles)H-Index: 1
Last. Ronald W. Busuttil (UCLA: University of California, Los Angeles)H-Index: 97
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Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer related death worldwide. Liver resection or transplantation is curative for a subset of patients with localized disease, but treatments for advanced disease are generally toxic and ineffective. Aberrant expression of the vascular endothelial growth factor (VEGF) has been implicated in the progression of HCC and represents a valid target for anticancer therapy. Bevacizumab, a humanized anti-VEGF monoclonal antibody,...
20 CitationsSource
#1Ramesh K. Ramanathan (University of Pittsburgh)H-Index: 43
#2Chandra P. Belani (University of Pittsburgh)H-Index: 59
Last. David R. Gandara (UC Davis: University of California, Davis)H-Index: 76
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Purpose To evaluate the response to lapatinib, an inhibitor of epidermal growth factor receptors 1 and 2, in patients with advanced bilary tree cancer (BTC) and hepatocellular cancer (HCC).
169 CitationsSource
#1Stephen H. Caldwell (University of Virginia Health System)H-Index: 52
#2Sang H. Park (Hallym University)H-Index: 1
The epidemiology of hepatocellular cancer (HCC) can be viewed from several important perspectives. The conventional perspective includes the overall public health impact of HCC, which is increasing in incidence in many regions of the world. The epidemiology of HCC can also be viewed from the perspective of variation in underlying disease associations such as viral hepatitis or the recently recognized link to nonalcoholic fatty liver disease (NAFLD). Of perhaps increasing importance with recent a...
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Cited By44
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Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide. Current treatment option for inoperable HCCs have decreased therapeutic efficacy and are associated with systemic toxicity and chemoresistance. Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide–dependent enzyme which is frequently overexpressed in HCC, where it promotes tumorigenicity, metastasis, and chemoresistance. SIRT1 also maintains the tumorigenic and self-renewal proprieties of liver...
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#1Hao Chen ('SMMU': Second Military Medical University)H-Index: 3
#2Xiao Yang ('SMMU': Second Military Medical University)H-Index: 1
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Abstract A series of α-santonin-derived compounds as potentially anti-hepatoma agents were designed and synthesized in an effort to find novel therapeutic agents. Among them, derivative 5h was more potent than the positive control 5-fluorouracil (5-Fu) on HepG-2, QGY-7703 and SMMC-7721 with IC50 values of 7.51, 3.06 and 4.08 μM, respectively. The structure-activity relationships (SARs) of these derivatives were discussed. In addition, flow cytometry and western blot assay revealed that the deriv...
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#2Meimei WuH-Index: 1
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AbstractAt present, the chemotherapy of advanced inoperable liver cancer is limited with serious side effects. Curcumin possesses multiple cancer preventive activities and low safety concerns. However, its poor solubility and instability in water pose significant pharmacological barriers to its clinical application. In this study, we presented a novel delivery system – the glycyrrhetinic acid modified curcumin-loaded cationic liposomes (GAMCLCL) and investigated its antitumor activities on HepG2...
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#1Kai-Li Jian (CPU: China Pharmaceutical University)H-Index: 6
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ABSTRACT Background Eucalyptus extracts have anti-cancer activity against various cancer cells. Formyl-phloroglucinol meroterpenoids (FPMs), which are typical secondary metabolites of the genera Eucalyptus, have many important pharmacological activities. Purpose Eucalrobusone C (EC), a new bioactive phytochemical, was first isolated from the leaves of Eucalyptus robusta in our laboratory. EC is a FPM, and our previous research revealed that EC showed strongest cytotoxicity in three cancer models...
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Background Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer death worldwide. It is a heterogeneous disorder and >80 % of the tumors develop in patients with liver cirrhosis, resulting from chronic inflammation and/or fibrosis. Here, we set out to identify novel targets for HCC therapy and to define a subgroup of patients that might benefit most from it.
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#1Zeng LiH-Index: 1
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Objective(s): We previously reported a series of quinazoline derivatives as vascular-targeting anticancer agents. In this study, we investigated the mechanism underlying the anti-angiogenic activity of the quinazoline derivative compound 11d. Materials and Methods: We examined the effects of quinazoline derivative 11d on vascular endothelial growth factor receptor-2 (VEGFR2) activation via VEGFR2-specific activation assay. Reverse transcription and immunohistochemistry were used to detect vascul...
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#1Nadia Ferlazzo (UNIME: University of Messina)H-Index: 21
#2Santa Cirmi (UNIME: University of Messina)H-Index: 14
Last. Michele Navarra (UNIME: University of Messina)H-Index: 29
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Abstract Aims Among cancers, hepatocellular carcinoma is one of the commonest worldwide, and its incidence is increasing around the world. A lot of evidence underlines that natural substances usually consumed in the diet can have an important role in the prevention of cancer. In this study we investigated the molecular mechanisms underlying the antiproliferative activity of Citrus bergamia (bergamot) juice (BJ) in human hepatocellular carcinoma HepG2 cells. Main methods HepG2 cells were exposed ...
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