Targeting HSP90 in ovarian cancers with multiple receptor tyrosine kinase coactivation
<p>Abstract</p> <p>Background</p> <p>Ovarian cancer has the highest mortality rate of all gynecologic malignancy. The receptor tyrosine kinases (RTKs), including EGFR, ERBB2, PDGFR, VEGFR and MET, are activated in subsets of ovarian cancer, suggesting that these kinases...
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| 格式: | 文件 |
| 语言: | English |
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BMC
2011-09-01
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| 丛编: | Molecular Cancer |
| 主题: | |
| 在线阅读: | http://www.molecular-cancer.com/content/10/1/125 |
| _version_ | 1828947175650885632 |
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| author | Zhou Haimeng Meng Fanguo Ou Wenbin Jiao Yisheng Wang Aiyuan |
| author_facet | Zhou Haimeng Meng Fanguo Ou Wenbin Jiao Yisheng Wang Aiyuan |
| author_sort | Zhou Haimeng |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Ovarian cancer has the highest mortality rate of all gynecologic malignancy. The receptor tyrosine kinases (RTKs), including EGFR, ERBB2, PDGFR, VEGFR and MET, are activated in subsets of ovarian cancer, suggesting that these kinases might represent novel therapeutic targets. However, clinical trials have not or just partially shown benefit to ovarian cancers treated with EGFR, ERBB2, or PDGFR inhibitors. Despite multiple RTK activation in ovarian cancer pathogenesis, it is unclear whether transforming activity is dependent on an individual kinase oncoprotein or the coordinated activity of multiple kinases. We hypothesized that a coordinated network of multi-RTK activation is important for the tumorigenesis of ovarian cancers.</p> <p>Results</p> <p>Herein, we demonstrate co-activation of multiple RTKs (EGFR, ERBB2, ERBB4, MET and/or AXL) in individual ovarian cancer cell lines and primary tumors. We also show that coordinate inhibition of this multi-kinase signaling has substantially greater effect on ovarian cancer proliferation and survival, compared to inhibition of individual activated kinases. The inhibition of this multi-RTK signaling by HSP90 suppression results in profound pro-apoptotic and anti-proliferative effects, and is associated with the inactivation of RTK downstream PI3-K/AKT/mTOR and RAF/MAPK signaling.</p> <p>Conclusion</p> <p>These studies suggest that anti-multiple RTK strategy could be useful in the treatment of ovarian cancer.</p> |
| first_indexed | 2024-12-14T05:23:33Z |
| format | Article |
| id | doaj.art-ccf0178bbf2f4d2d9211a8dc28a63bcf |
| institution | Directory Open Access Journal |
| issn | 1476-4598 |
| language | English |
| last_indexed | 2024-12-14T05:23:33Z |
| publishDate | 2011-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj.art-ccf0178bbf2f4d2d9211a8dc28a63bcf2022-12-21T23:15:36ZengBMCMolecular Cancer1476-45982011-09-0110112510.1186/1476-4598-10-125Targeting HSP90 in ovarian cancers with multiple receptor tyrosine kinase coactivationZhou HaimengMeng FanguoOu WenbinJiao YishengWang Aiyuan<p>Abstract</p> <p>Background</p> <p>Ovarian cancer has the highest mortality rate of all gynecologic malignancy. The receptor tyrosine kinases (RTKs), including EGFR, ERBB2, PDGFR, VEGFR and MET, are activated in subsets of ovarian cancer, suggesting that these kinases might represent novel therapeutic targets. However, clinical trials have not or just partially shown benefit to ovarian cancers treated with EGFR, ERBB2, or PDGFR inhibitors. Despite multiple RTK activation in ovarian cancer pathogenesis, it is unclear whether transforming activity is dependent on an individual kinase oncoprotein or the coordinated activity of multiple kinases. We hypothesized that a coordinated network of multi-RTK activation is important for the tumorigenesis of ovarian cancers.</p> <p>Results</p> <p>Herein, we demonstrate co-activation of multiple RTKs (EGFR, ERBB2, ERBB4, MET and/or AXL) in individual ovarian cancer cell lines and primary tumors. We also show that coordinate inhibition of this multi-kinase signaling has substantially greater effect on ovarian cancer proliferation and survival, compared to inhibition of individual activated kinases. The inhibition of this multi-RTK signaling by HSP90 suppression results in profound pro-apoptotic and anti-proliferative effects, and is associated with the inactivation of RTK downstream PI3-K/AKT/mTOR and RAF/MAPK signaling.</p> <p>Conclusion</p> <p>These studies suggest that anti-multiple RTK strategy could be useful in the treatment of ovarian cancer.</p>http://www.molecular-cancer.com/content/10/1/125Ovarian CancerTyrosine KinasescoactivationHSP90 |
| spellingShingle | Zhou Haimeng Meng Fanguo Ou Wenbin Jiao Yisheng Wang Aiyuan Targeting HSP90 in ovarian cancers with multiple receptor tyrosine kinase coactivation Molecular Cancer Ovarian Cancer Tyrosine Kinases coactivation HSP90 |
| title | Targeting HSP90 in ovarian cancers with multiple receptor tyrosine kinase coactivation |
| title_full | Targeting HSP90 in ovarian cancers with multiple receptor tyrosine kinase coactivation |
| title_fullStr | Targeting HSP90 in ovarian cancers with multiple receptor tyrosine kinase coactivation |
| title_full_unstemmed | Targeting HSP90 in ovarian cancers with multiple receptor tyrosine kinase coactivation |
| title_short | Targeting HSP90 in ovarian cancers with multiple receptor tyrosine kinase coactivation |
| title_sort | targeting hsp90 in ovarian cancers with multiple receptor tyrosine kinase coactivation |
| topic | Ovarian Cancer Tyrosine Kinases coactivation HSP90 |
| url | http://www.molecular-cancer.com/content/10/1/125 |
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