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Sorafenib

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Novel piperazine-chalcone hybrids and related pyrazoline analogues targeting VEGFR-2 kinase; design, synthesis, molecular docking studies, and anticancer evaluation.

Marwa F Ahmed, Eman Y Santali, Radwan El-Haggar,

New piperazine-chalcone hybrids and related pyrazoline derivatives have been designed and synthesised as potential vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitors. The National Cancer Institute (NCI) has selected six compounds to evaluate their antiproliferative activity <i>in vitro</i> against 60 human cancer cells lines. Preliminary screening of the examined compounds indicated promising ... Read more >>

J Enzyme Inhib Med Chem (Journal of enzyme inhibition and medicinal chemistry)
[2021, 36(1):307-318]

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3-Methyladenine-enhanced susceptibility to sorafenib in hepatocellular carcinoma cells by inhibiting autophagy.

Fangfang Zhao, Guohe Feng, Junyao Zhu, Zhijun Su, Ruyi Guo, Jiangfu Liu, Huatang Zhang, Yongzhen Zhai,

As an effective targeted therapy for advanced hepatocellular carcinoma (HCC), sorafenib resistance has been frequently reported in recent years, with the activation of autophagy by cancer cells under drug stress being one of the crucial reasons. Sorafenib treatment could enhance autophagy in HCC cells and autophagy is also considered as ... Read more >>

Anticancer Drugs (Anti-cancer drugs)
[2021, 32(4):386-393]

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Sorafenib combined with dasatinib therapy inhibits cell viability, migration, and angiogenesis synergistically in hepatocellular carcinoma.

Chiung-Chi Cheng, Wei-Ting Chao, Jing-Hao Shih, Yih-Shyong Lai, Yung-Hsiang Hsu, Yi-Hsiang Liu,

<h4>Purpose</h4>Sorafenib is a multikinase inhibitor used for treatment of advanced hepatocellular carcinoma. Sorafenib resistance may be related to Src-induced cell migration and angiogenesis, which are regulated by cancer stem cell activation and release of vascular endothelial growth factor. Dasatinib is a Src inhibitor that inhibits Src phosphorylation and suppresses Src-associated ... Read more >>

Cancer Chemother Pharmacol (Cancer chemotherapy and pharmacology)
[2021, :]

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Role of ATP-binding Cassette Transporters in Sorafenib Therapy for Hepatocellular Carcinoma: an overview.

Maria Manuela Estevinho, Carlos Fernandes, João Carlos Silva, Ana Catarina Gomes, Edgar Afecto, João Correia, João Carvalho,

<h4>Background</h4>Molecular therapy with sorafenib remains the mainstay for advanced-stage hepatocellular carcinoma. Notwithstanding, treatment efficacy is low, with few patients obtaining long-lasting benefits due to the high chemoresistance rate.<h4>Objective</h4>To perform, for the first time, an overview of the literature concerning the role of adenosine triphosphate-binding cassette (ABC) transporters in sorafenib therapy ... Read more >>

Curr Drug Targets (Current drug targets)
[2021, :]

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Efficacy of Ramucirumab Versus Sorafenib as Subsequent Treatment for Hepatocellular Carcinoma.

Kazuki Maesaka, Ryotaro Sakamori, Ryoko Yamada, Yuki Tahata, Kazuyoshi Ohkawa, Masahide Oshita, Shinji Tamura, Hideki Hagiwara, Eiji Mita, Takayuki Yakushijin, Masami Inada, Takahiro Kodama, Hayato Hikita, Tomohide Tatsumi, Tetsuo Takehara,

<h4>Background/aim</h4>The present study aimed to examine the therapeutic efficacy of ramucirumab compared with that of sorafenib as subsequent systemic therapy for patients with hepatocellular carcinoma (HCC) and serum α-fetoprotein (AFP) levels ≥400 ng/ml.<h4>Patients and methods</h4>In our prospectively registered, real-world cohort, 13 and 11 patients treated with ramucirumab or sorafenib, respectively, ... Read more >>

Anticancer Res (Anticancer research)
[2021, 41(4):2187-2192]

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The Ribosomal Protein L28 Gene Is Involved in Sorafenib Resistance in Hepatocellular Carcinoma

Yi Shi, Xiaojiang Wang, Qiong Zhu, Gang Chen,

<h4>Background: </h4> Sorafenib is the first molecular-targeted drug for the treatment of advanced hepatocellular carcinoma (HCC). However, its treatment efficiency decreases after a short period of time because of the development of drug resistance. This study investigates the role of key genes in regulating sorafenib-resistance in hepatocellular carcinoma and elucidates ... Read more >>

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Herbal formula of Bushen Jianpi combined with sorafenib inhibits hepatocellular carcinoma growth by promoting cell apoptosis and blocking the cell cycle.

Zhangjie Zhou, Xinhua Liu, Tingting Wu, Zujue Que, Zhonghua Wu, Weizhong Wu, Shujuan Fu, Shiqiang Zhang, Yun Yang, Haiyan Jiang, Xiaoting Xia, Junqiang Lv, Boqian Du, Yun Li, Tao Lu, Zhihui Zhang, Yi Zhong,

<h4>Objective</h4>To investigate the efficacy of an herbal formula of Bushen Jianpi ( BSJP) combined with sorafenib on hepatocellular carcinoma (HCC) in vitro and in vivo, and to study the underlying mechanisms of action.<h4>Methods</h4>BSJP, a mixture of 12 raw herbs, was extracted in 70% alcohol/30% water and freeze-dried into a powder. ... Read more >>

J Tradit Chin Med (Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan)
[2021, 41(2):194-202]

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SPARC regulates ferroptosis induced by sorafenib in human hepatocellular carcinoma.

Hong-Wei Hua, Hao-Sheng Jiang, Ling Jia, Yi-Ping Jia, Yu-Lan Yao, Yi-Wen Chen, Feng Jiang, Dong-Qing Lu, Qing Zhou, Ma-Wei Jiang, Gang Ding,

<h4>Background</h4>Secreted protein acidic and rich in cysteine (SPARC) is implicated in cancer progression, but its role and associated molecular mechanism in the sorafenib sensitivity of hepatocellular carcinoma cells (HCC) remains elusive.<h4>Methods</h4>Human HCC cell lines Hep3B and HepG2 were treated with sorafenib alone or combined with activator or inhibitor of ferroptosis. ... Read more >>

Cancer Biomark (Cancer biomarkers : section A of Disease markers)
[2021, :]

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Comparative Efficacy of Cabozantinib and Ramucirumab After Sorafenib for Patients with Hepatocellular Carcinoma and Alpha-fetoprotein ≥ 400 ng/mL: A Matching-Adjusted Indirect Comparison.

Jörg Trojan, Patrick Mollon, Bruno Daniele, Florence Marteau, Lidia Martín, Yuxin Li, Qing Xu, Fabio Piscaglia, Renata Zaucha, Debashis Sarker, Ho Yeong Lim, Marino Venerito,

<h4>Introduction</h4>Cabozantinib and ramucirumab are approved for the treatment of adults with hepatocellular carcinoma (HCC) following prior sorafenib treatment; ramucirumab is restricted to use in patients with serum alpha-fetoprotein (AFP) ≥ 400 ng/mL. This matching-adjusted indirect comparison evaluated the efficacy and safety of both drugs after sorafenib in patients with HCC and AFP ≥ 400 ng/mL.<h4>Methods</h4>Individual patient ... Read more >>

Adv Ther (Advances in therapy)
[2021, :]

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Enhanced anticancer activity by the combination of vinpocetine and sorafenib via PI3K/AKT/GSK-3β signaling axis in hepatocellular carcinoma cells.

Zuo-Yan Zhang, Shu-Min Dong, Ye-Han Liu, Man-Man Zhang, Jian-Kang Zhang, Hua-Jian Zhu, Jia-An Shao, Hua-Qing Liu, Yang-Ling Li, Chong Zhang, Ling-Hui Zeng,

Vinpocetine is widely used to treat cerebrovascular diseases. However, the effect of vinpocetine to treat hepatocellular carcinoma (HCC) has not been investigated. In this study, we revealed that vinpocetine was associated with antiproliferative activity in HCC cells, but induced cytoprotective autophagy, which restricted its antitumor activity. Autophagy inhibitors improved the ... Read more >>

Anticancer Drugs (Anti-cancer drugs)
[2021, :]

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eIF4E-eIF4G complex inhibition synergistically enhances the effect of sorafenib in hepatocellular carcinoma.

Chao Fang, Haishen Xie, Jun Zhao, Weichen Wang, Hui Hou, Bin Zhang, Xiaoping Geng, Dachen Zhou,

<h4>Objective</h4>The clinical efficacy of sorafenib in hepatocellular carcinoma (HCC) is disappointing due to its low response rate and high rates of adverse effects. The eukaryotic translation initiation factor 4F (eIF4F) complex, mainly consisting of eIF4E-eukaryotic translation initiation factor 4G (eIF4G) interaction, is involved in the induction of drug resistance. Herein, ... Read more >>

Anticancer Drugs (Anti-cancer drugs)
[2021, :]

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Erratum: Oridonin Sensitizes Hepatocellular Carcinoma to the Anticancer Effect of Sorafenib by Targeting the Akt Pathway [Corrigendum].

[This corrects the article DOI: 10.2147/CMAR.S257482.]. ... Read more >>

Cancer Manag Res (Cancer management and research)
[2021, 13:2515]

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Association of Albumin-Bilirubin Grade and Sequential Treatment with Standard Systemic Therapies for Advanced Hepatocellular Carcinoma: A Retrospective Cohort Study Using a Japanese Administrative Database.

Atsushi Hiraoka, Yoshinori Tanizawa, Yu-Jing Huang, Zhihong Cai, Sachi Sakaguchi,

<h4>Background</h4>Evidence about the relationship between albumin-bilirubin (ALBI) grade and sequential systemic therapy for advanced hepatocellular carcinoma in real-world Japanese clinical practice is limited.<h4>Objective</h4>The objective of this study was to investigate ALBI grades and sequential treatment for advanced hepatocellular carcinoma in Japanese clinical practice.<h4>Methods</h4>We conducted a retrospective cohort study using a ... Read more >>

Drugs Real World Outcomes (Drugs - real world outcomes)
[2021, :]

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Current status of sorafenib nanoparticle delivery systems in the treatment of hepatocellular carcinoma.

Fan-Hua Kong, Qi-Fa Ye, Xiong-Ying Miao, Xi Liu, Si-Qi Huang, Li Xiong, Yu Wen, Zi-Jian Zhang,

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and one of the leading causes of cancer-related death worldwide. Advanced HCC displays strong resistance to chemotherapy, and traditional chemotherapy drugs do not achieve satisfactory therapeutic efficacy. Sorafenib is an oral kinase inhibitor that inhibits tumor cell proliferation and ... Read more >>

Theranostics (Theranostics)
[2021, 11(11):5464-5490]

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Artesunate Regulates Neurite Outgrowth Inhibitor Protein B Receptor to Overcome Resistance to Sorafenib in Hepatocellular Carcinoma Cells.

Wubin He, Xiaoxu Huang, Bradford K Berges, Yue Wang, Ni An, Rongjian Su, Yanyan Lu,

The multireceptor tyrosine kinase inhibitor sorafenib is a Food and Drug Administration-approved first-line drug for the treatment of advanced liver cancer that can reportedly extend overall survival in patients with advanced hepatocellular carcinoma (HCC). Primary and acquired resistance to sorafenib are gradually increasing however, leading to failure of HCC treatment ... Read more >>

Front Pharmacol (Frontiers in pharmacology)
[2021, 12:615889]

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Cost-effectiveness of Atezolizumab Plus Bevacizumab vs Sorafenib for Patients With Unresectable or Metastatic Hepatocellular Carcinoma.

Xin Zhang, Jingjing Wang, Juanjuan Shi, Xiaoli Jia, Shuangsuo Dang, Wenjun Wang,

<h4>Importance</h4>Atezolizumab plus bevacizumab as a first-line therapy for patients with unresectable or metastatic hepatocellular carcinoma has been shown to improve overall and progression-free survival compared with standard sorafenib treatment. However, because of the high cost of atezolizumab plus bevacizumab, assessment of its value by considering both efficacy and cost is ... Read more >>

JAMA Netw Open (JAMA network open)
[2021, 4(4):e214846]

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YAP promotes sorafenib resistance in hepatocellular carcinoma by upregulating survivin.

Ting Sun, Wenhao Mao, Hui Peng, Qi Wang, Lin Jiao,

<h4>Background</h4>Sorafenib is the standard first-line treatment for advanced hepatocellular carcinoma (HCC), but its use is hampered by secondary drug resistance. Yes-associated protein (YAP) is a downstream effector of the Hippo signaling pathway, which is crucial for liver tumorigenesis. As yet, however, the mechanism underlying sorafenib resistance and the role of ... Read more >>

Cell Oncol (Dordr) (Cellular oncology (Dordrecht))
[2021, :]

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The Cost-Effectiveness of Lenvatinib in the Treatment of Advanced or Unresectable Hepatocellular Carcinoma from a Canadian Perspective.

Brandon M Meyers, Arndt Vogel, Paul Marotta, Petr Kavan, Laveena Kamboj, Janice Pan, Marc Geadah, David Trueman, Suthakar Sabapathy,

Lenvatinib is an oral multikinase inhibitor indicated for the first-line treatment of unresectable hepatocellular carcinoma (uHCC). In the Phase III REFLECT trial, lenvatinib was noninferior in the primary endpoint of overall survival versus sorafenib, the only systemic therapy funded in Canada prior to the introduction of lenvatinib. Lenvatinib also demonstrated ... Read more >>

Can J Gastroenterol Hepatol (Canadian journal of gastroenterology & hepatology)
[2021, 2021:8811018]

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TKI Maintenance After Stem-Cell Transplantation for FLT3-ITD Positive Acute Myeloid Leukemia: A Systematic Review and Meta-Analysis.

Nico Gagelmann, Christine Wolschke, Evgeny Klyuchnikov, Maximilian Christopeit, Francis Ayuk, Nicolaus Kröger,

This analysis aimed to systematically review and synthesize the existing evidence regarding the outcome of tyrosine kinase inhibitor (TKI) maintenance therapy after allogeneic stem-cell transplantation for patients with <i>FLT3</i>-ITD-mutated acute myeloid leukemia (AML). We searched publicly available databases, references lists of relevant reviews, registered trials, and relevant conference proceedings. A ... Read more >>

Front Immunol (Frontiers in immunology)
[2021, 12:630429]

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Simultaneous Determination of Nine Residual Solvents in Sorafenib Tosylate by Gas Chromatography.

Rong Sun, Chengran Hu, Qian Dou, Libiao Luan,

<h4>Background</h4>The direct injection gas chromatography is convenient and quick, and the residual solvent with a higher boiling point can be measured, which is developed for residual solvents analysis of Sorafenib Tosylate.<h4>Objective</h4>In the present investigation, the injection method was developed and validated for the detection and quantification of residual solvents in ... Read more >>

J AOAC Int (Journal of AOAC International)
[2021, :]

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Maintenance therapy for FLT3-ITD-mutated acute myeloid leukemia.

Andreas Burchert,

FLT3-ITD is a constitutively activated variant of the FLT3 tyrosine kinase receptor. Its expression in acute myeloid leukemia (AML) is associated with a poor prognosis. Due to this, the development of tyrosine kinase inhibitors (TKI) blocking FLT3-ITD became a rational therapeutic concept. This review describes key milestones in the clinical ... Read more >>

Haematologica (Haematologica)
[2021, 106(3):664-670]

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Proposal of a prediction model describing the metabolic interaction between warfarin and sorafenib using a population pharmacokinetic approach.

Kazuhiko Asari, Harumi Takahashi,

<h4>Objective</h4>We attempted to examine the applicability of a population pharmacokinetic-pharmacodynamic (PK-PD) model describing the metabolic interaction between warfarin and sorafenib due to CYP2C9 inhibition and to predict the plasma concentrations of sorafenib and S-warfarin, the international normalized ratio (INR), and the optimal maintenance dose of warfarin in the presence of ... Read more >>

Int J Clin Pharmacol Ther (International journal of clinical pharmacology and therapeutics)
[2021, 59(3):202-215]

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Synthesis of sorafenib analogues incorporating a 1,2,3-triazole ring and cytotoxicity towards hepatocellular carcinoma cell lines.

Sarinya Palakhachane, Yuwaporn Ketkaew, Natthaya Chuaypen, Jitnapa Sirirak, Jutatip Boonsombat, Somsak Ruchirawat, Pisit Tangkijvanich, Apichart Suksamrarn, Panupun Limpachayaporn,

A series of 1,2,3-triazole-containing Sorafenib analogues, in which the aryl urea moiety of Sorafenib (1) was replaced with a 1,2,3-triazole ring linking a substituted phenoxy fragment, were prepared successfully via Huisgen 1,3-dipolar cycloaddition and nucleophilic aromatic substitution. The studies of cytotoxicity towards human hepatocellular carcinoma (HCC) cell lines, HepG2 and ... Read more >>

Bioorg Chem (Bioorganic chemistry)
[2021, 112:104831]

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Baseline Interleukin-6 and -8 predict response and survival in patients with advanced hepatocellular carcinoma treated with sorafenib monotherapy: an exploratory post hoc analysis of the SORAMIC trial.

Osman Öcal, Kerstin Schütte, Juozas Kupčinskas, Egidijus Morkunas, Gabija Jurkeviciute, Enrico N de Toni, Najib Ben Khaled, Thomas Berg, Peter Malfertheiner, Heinz Josef Klümpen, Christian Sengel, Bristi Basu, Juan W Valle, Julia Benckert, Antonio Gasbarrini, Daniel Palmer, Ricarda Seidensticker, Moritz Wildgruber, Bruno Sangro, Maciej Pech, Jens Ricke, Max Seidensticker,

<h4>Purpose</h4>To explore the potential correlation between baseline interleukin (IL) values and overall survival or objective response in patients with hepatocellular carcinoma (HCC) receiving sorafenib.<h4>Methods</h4>A subset of patients with HCC undergoing sorafenib monotherapy within a prospective multicenter phase II trial (SORAMIC, sorafenib treatment alone vs. combined with Y90 radioembolization) underwent baseline ... Read more >>

J Cancer Res Clin Oncol (Journal of cancer research and clinical oncology)
[2021, :]

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Cucurbitacin B exhibits antitumor effects on CD133+ HepG2 liver cancer stem cells by inhibiting JAK2/STAT3 signaling pathway.

Xiaoli Wang, Yudi Bai, Xue Yan, Jin Li, Bingxue Lin, Linzhi Dai, Cheng Xu, Hua Li, Dong Li, Tai Yang, Tao Zhang,

Cancer stem cells (CSCs), a crucial cancer cell subpopulation, possess stemness phenotypic characteristics. Cucurbitacin B (CuB), a tetracyclic triterpenoid isolated from Cucurbitaceae, exerts widely pharmacological activities in many diseases. The aim of this study was to enrich, identify liver CSCs and investigate antitumor effects of CuB as well as explore ... Read more >>

Anticancer Drugs (Anti-cancer drugs)
[2021, 32(5):548-557]

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