New knowledge of the mechanisms of sorafenib resistance in liver cancer

Sorafenib is an oral multikinase inhibitor that suppresses tumor cell proliferation and angiogenesis and promotes tumor cell apoptosis It was approved by the FDA for the treatment of advanced renal cell carcinoma in 2006, and as a unique target drug for advanced hepatocellular carcinoma （HCC） in 200...

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Published in:	Acta pharmacologica Sinica Vol. 38; no. 5; pp. 614 - 622
Main Authors:	Zhu, Yan-jing, Zheng, Bo, Wang, Hong-yang, Chen, Lei
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 01.05.2017 Nature Publishing Group
Subjects:	Antineoplastic Agents - therapeutic use Biomedical and Life Sciences Biomedicine Carcinoma, Hepatocellular - drug therapy Drug Resistance, Neoplasm Epithelial-Mesenchymal Transition Humans Immunology Internal Medicine Liver cancer Liver Neoplasms - drug therapy Medical Microbiology Niacinamide - administration & dosage Niacinamide - analogs & derivatives Niacinamide - therapeutic use Pharmacology/Toxicology Phenylurea Compounds - administration & dosage Phenylurea Compounds - therapeutic use Protein Kinase Inhibitors - therapeutic use Review Vaccine individualized treatment targeted therapy drug resistance sorafenib hepatocellular carcinoma
ISSN:	1671-4083, 1745-7254, 1745-7254
Online Access:	Get full text
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Abstract	Sorafenib is an oral multikinase inhibitor that suppresses tumor cell proliferation and angiogenesis and promotes tumor cell apoptosis It was approved by the FDA for the treatment of advanced renal cell carcinoma in 2006, and as a unique target drug for advanced hepatocellular carcinoma （HCC） in 2007. Sorafenib can significantly extend the median survival time of patients but only by 3-5 months. Moreover, it is associated with serious adverse side effects, and drug resistance often develops. Therefore, it is of great importance to explore the mechanisms underlying sorafenib resistance and to develop individualized therapeutic strategies for coping with these problems. Recent studies to the primary resistance, mechanisms are underying the acquired resistance to sorafenib, such as crosstalk involving PI3K/Akt and JAK-STAT pathways, the activation of hypoxia-inducible pathways, and epithelial-mesenchymal transition. Here, we briefly describe the function of sorafenib, its clinical application, and the molecular mechanisms for drug resistance, especially for HCC patients.
AbstractList	Sorafenib is an oral multikinase inhibitor that suppresses tumor cell proliferation and angiogenesis and promotes tumor cell apoptosis It was approved by the FDA for the treatment of advanced renal cell carcinoma in 2006, and as a unique target drug for advanced hepatocellular carcinoma （HCC） in 2007. Sorafenib can significantly extend the median survival time of patients but only by 3-5 months. Moreover, it is associated with serious adverse side effects, and drug resistance often develops. Therefore, it is of great importance to explore the mechanisms underlying sorafenib resistance and to develop individualized therapeutic strategies for coping with these problems. Recent studies to the primary resistance, mechanisms are underying the acquired resistance to sorafenib, such as crosstalk involving PI3K/Akt and JAK-STAT pathways, the activation of hypoxia-inducible pathways, and epithelial-mesenchymal transition. Here, we briefly describe the function of sorafenib, its clinical application, and the molecular mechanisms for drug resistance, especially for HCC patients. Sorafenib is an oral multikinase inhibitor that suppresses tumor cell proliferation and angiogenesis and promotes tumor cell apoptosis. It was approved by the FDA for the treatment of advanced renal cell carcinoma in 2006, and as a unique target drug for advanced hepatocellular carcinoma (HCC) in 2007. Sorafenib can significantly extend the median survival time of patients but only by 3-5 months. Moreover, it is associated with serious adverse side effects, and drug resistance often develops. Therefore, it is of great importance to explore the mechanisms underlying sorafenib resistance and to develop individualized therapeutic strategies for coping with these problems. Recent studies have revealed that in addition to the primary resistance, several mechanisms are underlying the acquired resistance to sorafenib, such as crosstalk involving PI3K/Akt and JAK-STAT pathways, the activation of hypoxia-inducible pathways, and epithelial-mesenchymal transition. Here, we briefly describe the function of sorafenib, its clinical application, and the molecular mechanisms for drug resistance, especially for HCC patients. Sorafenib is an oral multikinase inhibitor that suppresses tumor cell proliferation and angiogenesis and promotes tumor cell apoptosis. It was approved by the FDA for the treatment of advanced renal cell carcinoma in 2006, and as a unique target drug for advanced hepatocellular carcinoma (HCC) in 2007. Sorafenib can significantly extend the median survival time of patients but only by 3-5 months. Moreover, it is associated with serious adverse side effects, and drug resistance often develops. Therefore, it is of great importance to explore the mechanisms underlying sorafenib resistance and to develop individualized therapeutic strategies for coping with these problems. Recent studies have revealed that in addition to the primary resistance, several mechanisms are underlying the acquired resistance to sorafenib, such as crosstalk involving PI3K/Akt and JAK-STAT pathways, the activation of hypoxia-inducible pathways, and epithelial-mesenchymal transition. Here, we briefly describe the function of sorafenib, its clinical application, and the molecular mechanisms for drug resistance, especially for HCC patients.Sorafenib is an oral multikinase inhibitor that suppresses tumor cell proliferation and angiogenesis and promotes tumor cell apoptosis. It was approved by the FDA for the treatment of advanced renal cell carcinoma in 2006, and as a unique target drug for advanced hepatocellular carcinoma (HCC) in 2007. Sorafenib can significantly extend the median survival time of patients but only by 3-5 months. Moreover, it is associated with serious adverse side effects, and drug resistance often develops. Therefore, it is of great importance to explore the mechanisms underlying sorafenib resistance and to develop individualized therapeutic strategies for coping with these problems. Recent studies have revealed that in addition to the primary resistance, several mechanisms are underlying the acquired resistance to sorafenib, such as crosstalk involving PI3K/Akt and JAK-STAT pathways, the activation of hypoxia-inducible pathways, and epithelial-mesenchymal transition. Here, we briefly describe the function of sorafenib, its clinical application, and the molecular mechanisms for drug resistance, especially for HCC patients.
Author	Yan-jing ZHU Bo ZHENG Hong-yang WANG Lei CHEN
AuthorAffiliation	International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, China National Center for Liver Cancer, Shanghai 201805, China
Author_xml	– sequence: 1 givenname: Yan-jing surname: Zhu fullname: Zhu, Yan-jing organization: International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University – sequence: 2 givenname: Bo surname: Zheng fullname: Zheng, Bo organization: International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University – sequence: 3 givenname: Hong-yang surname: Wang fullname: Wang, Hong-yang email: hywangk@vip.sina.com organization: International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, National Center for Liver Cancer – sequence: 4 givenname: Lei surname: Chen fullname: Chen, Lei email: chenlei@smmu.edu.cn organization: International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, National Center for Liver Cancer
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/28344323$$D View this record in MEDLINE/PubMed
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Notes	Sorafenib is an oral multikinase inhibitor that suppresses tumor cell proliferation and angiogenesis and promotes tumor cell apoptosis It was approved by the FDA for the treatment of advanced renal cell carcinoma in 2006, and as a unique target drug for advanced hepatocellular carcinoma （HCC） in 2007. Sorafenib can significantly extend the median survival time of patients but only by 3-5 months. Moreover, it is associated with serious adverse side effects, and drug resistance often develops. Therefore, it is of great importance to explore the mechanisms underlying sorafenib resistance and to develop individualized therapeutic strategies for coping with these problems. Recent studies to the primary resistance, mechanisms are underying the acquired resistance to sorafenib, such as crosstalk involving PI3K/Akt and JAK-STAT pathways, the activation of hypoxia-inducible pathways, and epithelial-mesenchymal transition. Here, we briefly describe the function of sorafenib, its clinical application, and the molecular mechanisms for drug resistance, especially for HCC patients. sorafenib; hepatocellular carcinoma; targeted therapy; drug resistance; individualized treatment 31-1347/R ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Review-3 content type line 23 These authors contributed equally to this work.
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Snippet	Sorafenib is an oral multikinase inhibitor that suppresses tumor cell proliferation and angiogenesis and promotes tumor cell apoptosis It was approved by the... Sorafenib is an oral multikinase inhibitor that suppresses tumor cell proliferation and angiogenesis and promotes tumor cell apoptosis. It was approved by the...
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SubjectTerms	Antineoplastic Agents - therapeutic use Biomedical and Life Sciences Biomedicine Carcinoma, Hepatocellular - drug therapy Drug Resistance, Neoplasm Epithelial-Mesenchymal Transition Humans Immunology Internal Medicine Liver cancer Liver Neoplasms - drug therapy Medical Microbiology Niacinamide - administration & dosage Niacinamide - analogs & derivatives Niacinamide - therapeutic use Pharmacology/Toxicology Phenylurea Compounds - administration & dosage Phenylurea Compounds - therapeutic use Protein Kinase Inhibitors - therapeutic use Review Vaccine
Title	New knowledge of the mechanisms of sorafenib resistance in liver cancer
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