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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Vydané v:Acta pharmacologica Sinica Ročník 38; číslo 5; s. 614 - 622
Hlavní autori: Zhu, Yan-jing, Zheng, Bo, Wang, Hong-yang, Chen, Lei
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: London Nature Publishing Group UK 01.05.2017
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ISSN:1671-4083, 1745-7254, 1745-7254
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Shrnutí: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.
Bibliografia: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