Liver cancer, a large proportion of which is hepatocellular carcinoma(HCC), is diagnosed in more than 700000 people each year worldwide. Liver cancer is particularly prevalent in Asia, Sub-Saharan Africa and the South...Liver cancer, a large proportion of which is hepatocellular carcinoma(HCC), is diagnosed in more than 700000 people each year worldwide. Liver cancer is particularly prevalent in Asia, Sub-Saharan Africa and the South Pacific, where hepatitis B and hepatitis C infection rates are very high. However, due to resistance to chemotherapy, patients with intermediate and advanced-stage disease cannot benefit from this treatment. Clusterin, which is overexpressed in many different cancers, is a stress-induced cytoprotective protein that confers treatment resistance. Custirsen(OGX-011) is a novel 2'-methoxyethyl modified phosphorothioate antisense oligonucleotide that targets secretory clusterin protein expression and is currently in clinical trials for patients with different cancers. In recent years, a number of different clinical trials have been performed, and two phase Ⅲ clinical trials of custirsen evaluating combinations with chemotherapy in patients with metastatic castration-resistant prostate cancer and metastatic non-small cell lung cancer are currently in progress. The aims of this review are to summarize the current state of research on clusterin, predict future research directions and analyze the potential of the clinical application of custirsen in HCC.展开更多
Defects within apoptotic pathways have been implicated in prostate cancer （PCa） tumorigenesis, metastatic progression and treatment resistance. A hallmark of cancers is the ability to derail apoptosis by inhibiting ...Defects within apoptotic pathways have been implicated in prostate cancer （PCa） tumorigenesis, metastatic progression and treatment resistance. A hallmark of cancers is the ability to derail apoptosis by inhibiting the apoptotic signal, reducing the expression of apoptotic proteins and/or amplifying survival signals through increased production of antiapoptotic molecule. This review describes associations between heat shock proteins （HSPs） and the human androgen receptor （AR）, the role of HSPs and other stress-induced proteins in PCa development and emerging strategies in targeting these protective proteins to treat PCa.展开更多
基金Supported by National Nature Science Foundation of China,No.81172331 and No.30972890Shandong Provincial Medicine and Health Science Technology Development Planning,China,No.2013WS0145
文摘Liver cancer, a large proportion of which is hepatocellular carcinoma(HCC), is diagnosed in more than 700000 people each year worldwide. Liver cancer is particularly prevalent in Asia, Sub-Saharan Africa and the South Pacific, where hepatitis B and hepatitis C infection rates are very high. However, due to resistance to chemotherapy, patients with intermediate and advanced-stage disease cannot benefit from this treatment. Clusterin, which is overexpressed in many different cancers, is a stress-induced cytoprotective protein that confers treatment resistance. Custirsen(OGX-011) is a novel 2'-methoxyethyl modified phosphorothioate antisense oligonucleotide that targets secretory clusterin protein expression and is currently in clinical trials for patients with different cancers. In recent years, a number of different clinical trials have been performed, and two phase Ⅲ clinical trials of custirsen evaluating combinations with chemotherapy in patients with metastatic castration-resistant prostate cancer and metastatic non-small cell lung cancer are currently in progress. The aims of this review are to summarize the current state of research on clusterin, predict future research directions and analyze the potential of the clinical application of custirsen in HCC.
文摘Defects within apoptotic pathways have been implicated in prostate cancer （PCa） tumorigenesis, metastatic progression and treatment resistance. A hallmark of cancers is the ability to derail apoptosis by inhibiting the apoptotic signal, reducing the expression of apoptotic proteins and/or amplifying survival signals through increased production of antiapoptotic molecule. This review describes associations between heat shock proteins （HSPs） and the human androgen receptor （AR）, the role of HSPs and other stress-induced proteins in PCa development and emerging strategies in targeting these protective proteins to treat PCa.
