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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Bibliographic Details
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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Summary: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.
Bibliography: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
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These authors contributed equally to this work.
ISSN:1671-4083
1745-7254
1745-7254
DOI:10.1038/aps.2017.5