Targeted therapy of hepatocellular cancer

Published on Feb 1, 2010in Expert Opinion on Investigational Drugs4.03
· DOI :10.1517/13543780903514110
Piotr J. Wysocki14
Estimated H-index: 14
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 (43)
Published on Jun 20, 2007in Journal of Clinical Oncology28.25
Celestia S. Higano59
Estimated H-index: 59
Evan Y. Yu30
Estimated H-index: 30
+ 6 AuthorsJonathan D. Schwartz22
Estimated H-index: 22
3505 Background: IMC-A12 is a fully human IgG1 monoclonal antibody directed against the human insulin like growth factor-I receptor. The safety and maximum tolerated dose (MTD) of IMC-A12 are being evaluated in an on-going a phase I trial. Methods: Patients (pts) with ECOG PS = 2 and advanced refractory solid tumors receive IMC-A12 weekly for 4 infusions per cycle until progression. After cycle one only, there is a two week observation period. Six cohorts of IMC-A12 are planned at 3, 6, 10, 15, ...
Published on Dec 12, 2016in Journal of Clinical Oncology28.25
J. Raoul8
Estimated H-index: 8
Richard S. Finn49
Estimated H-index: 49
+ 5 AuthorsIan Walters15
Estimated H-index: 15
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...
Published on Dec 1, 2009in BMC Cancer2.93
Zuo-Lin Xiang7
Estimated H-index: 7
(Fudan University),
Zhao-Chong Zeng15
Estimated H-index: 15
(Fudan University)
+ 5 AuthorsJian He7
Estimated H-index: 7
(Fudan University)
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.
Published on Oct 1, 2009in Archives of Pathology & Laboratory Medicine4.15
Young Nyun Park53
Estimated H-index: 53
Young-Bae Kim2
Estimated H-index: 2
+ 1 AuthorsChanil Park23
Estimated H-index: 23
Abstract Background.—Hepatocellular carcinoma (HCC) is known to receive its blood supply principally from the hepatic arteries. Recent studies have reported differences in the vascular supply, especially arterial supply among low- and high-grade dysplastic nodules (DNs) (also referred to as adenomatous hyperplasia and macroregenerative nodules) and HCCs. Increased expression of vascular endothelial growth factor (VEGF) has been reported in HCC. In addition, VEGF may play an important role in the...
Published on Sep 20, 2009in Journal of Clinical Oncology28.25
Shuji Ogino84
Estimated H-index: 84
Katsuhiko Nosho51
Estimated H-index: 51
+ 5 AuthorsCharles S. Fuchs124
Estimated H-index: 124
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...
Published on Sep 1, 2009in Cancer Chemotherapy and Pharmacology3.01
Ramesh K. Ramanathan43
Estimated H-index: 43
(University of Pittsburgh),
Chandra P. Belani57
Estimated H-index: 57
(University of Pittsburgh)
+ 11 AuthorsPhilip C. Mack38
Estimated H-index: 38
(UC Davis: University of California, Davis)
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).
Hung Huynh22
Estimated H-index: 22
K.H. Pierce Chow1
Estimated H-index: 1
(SGH: Singapore General Hospital)
+ 6 AuthorsEvelyn Tran4
Estimated H-index: 4
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...
Published on Jun 20, 2009in Journal of Clinical Oncology28.25
Andrew X Zhu A X64
Estimated H-index: 64
(Partners HealthCare),
Dushyant V. Sahani70
Estimated H-index: 70
+ 18 AuthorsJohanna Lahdenranta20
Estimated H-index: 20
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...
Published on Apr 1, 2009in Expert Opinion on Therapeutic Targets4.62
Abdul M. Oseini8
Estimated H-index: 8
(Mayo Clinic),
Lewis R. Roberts Mb ChB62
Estimated H-index: 62
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...
Published on Feb 20, 2009in Journal of Clinical Oncology28.25
Melanie B. Thomas22
Estimated H-index: 22
(University of Texas MD Anderson Cancer Center),
Jeffrey S. Morris51
Estimated H-index: 51
+ 7 AuthorsJames L. Abbruzzese104
Estimated H-index: 104
(University of Texas MD Anderson Cancer Center)
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...
Cited By43
Published on Jan 1, 2019in Frontiers in Nutrition
Marius Farcas , Andrei Gavrea + 4 AuthorsIoana Berindan-Neagoe23
Estimated H-index: 23
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...
Published on Apr 1, 2018in European Journal of Medicinal Chemistry4.83
Hao Chen4
Estimated H-index: 4
('SMMU': Second Military Medical University),
Xiao Yang ('SMMU': Second Military Medical University)+ 8 AuthorsQingyan Sun12
Estimated H-index: 12
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 IC 50 values of 7.51, 3.06 and 4.08 μ M, respectively. The structure-activity relationships (SARs) of these derivatives were discussed. In addition, flow cytometry and western blot assay revealed that the de...
Published on Jan 1, 2018in Drug Delivery3.83
Mingxiang Chang1
Estimated H-index: 1
(Hubei University of Chinese Medicine),
Meimei Wu1
Estimated H-index: 1
Hanmin Li1
Estimated H-index: 1
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...
Published on Dec 1, 2017in Cancer Cell International3.44
Tung Yueh Chuang4
Estimated H-index: 4
Hsiao Li Wu4
Estimated H-index: 4
+ 3 AuthorsYen Hao Chen5
Estimated H-index: 5
Background Hepatocellular carcinoma (HCC) is the seventh most common malignancy and the third leading cause of cancer-related death worldwide with an extremely grim prognosis. Berberine (BBR) has been found to inhibit proliferation of human HCC cells, although the underlying mechanism(s) are unclear.
Published on Feb 1, 2017in Phytomedicine4.18
Kai-Li Jian6
Estimated H-index: 6
(CPU: China Pharmaceutical University),
Chao Zhang12
Estimated H-index: 12
(CPU: China Pharmaceutical University)
+ 2 AuthorsLing-Yi Kong36
Estimated H-index: 36
(CPU: China Pharmaceutical University)
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...
Published on Dec 1, 2016in Cellular Oncology5.02
Vignesh Ramesh4
Estimated H-index: 4
(MKU: Madurai Kamaraj University),
Karthikeyan Selvarasu2
Estimated H-index: 2
(MKU: Madurai Kamaraj University)
+ 3 AuthorsKumaresan Ganesan10
Estimated H-index: 10
(MKU: Madurai Kamaraj University)
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.
Published on Dec 1, 2016in BMC Ophthalmology1.43
Julia Lüke5
Estimated H-index: 5
(University of Lübeck),
Vlatka Vukoja1
Estimated H-index: 1
(University of Lübeck)
+ 5 AuthorsAysegül Tura7
Estimated H-index: 7
(University of Lübeck)
Background Extracellular matrix remodelling regulated by matrix-metalloproteinase (MMP) inducer (CD147) is a crucial process during tumor cell invasion and regulation of blood supply. In this study, we evaluated the correlation of CD147 and MMP-2 expression with major prognostic factors for uveal melanoma and the development of metastasis.
Published on Aug 15, 2016in International Journal of Cancer4.98
Yan Zhao2
Estimated H-index: 2
(Fourth Military Medical University),
Hailiang Li2
Estimated H-index: 2
(Zhengzhou University)
+ 19 AuthorsWeixin Ren3
Estimated H-index: 3
(First Affiliated Hospital of Xinjiang Medical University)
The purpose of our study was to test the hypothesis that sorafenib-related dermatologic adverse events (AEs) as an early biomarker can predict the long-term outcomes following the combination therapy of transarterial chemoembolization (TACE) plus sorafenib (TACE-S). The intermediate-stage hepatocellular carcinoma patients who received either TACE-S or TACE-alone treatment were consecutively included into analysis. In the TACE-S group, patients with >= grade 2 dermatologic AEs within the first mo...
Published on Feb 1, 2016in Life Sciences3.45
Nadia Ferlazzo20
Estimated H-index: 20
(UNIME: University of Messina),
Santa Cirmi14
Estimated H-index: 14
(UNIME: University of Messina)
+ 6 AuthorsMichele Navarra25
Estimated H-index: 25
(UNIME: University of Messina)
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 ...
Published on Jan 1, 2016in Iranian Journal of Basic Medical Sciences1.85
Zeng Li1
Estimated H-index: 1
Bin Wang1
Estimated H-index: 1
+ 2 AuthorsJun Li1
Estimated H-index: 1
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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