Hsp90 as a therapeutic target in patients with oesophageal carcinoma
- 7 January 2010
- journal article
- review article
- Published by Taylor & Francis Ltd in Emerging Therapeutic Targets
- Vol. 14 (3), 317-328
- https://doi.org/10.1517/14728221003621278
Abstract
Oesophageal carcinoma has a poor prognosis with a 5-year overall survival rate of only 10 - 20%. The disease is often diagnosed at a late stage, when dissemination may already have occurred, contributing to the poor prognosis. However, recent developments in targeted therapy now offer new possibilities in the treatment arsenal. Heat shock protein 90 (Hsp90) has been demonstrated to protect oncogenic variants of signalling molecules from degradation, thus promoting cell growth and survival. Hsp90 has been found to be abundantly expressed in oesophageal cancer and may serve as a therapeutic target in the treatment of this disease. We have summarised available data concerning the role of Hsp90 in oesophageal carcinoma as well as available information on other tumour types. To be able to elaborate on the molecular mechanisms of action of Hsp90 and discuss state-of-the-art of clinical trials involving Hsp90 inhibitors in malignancies, with a special emphasis on oesophageal cancer. Preclinical studies on Hsp90 inhibition in oesophageal cancer are promising and it is anticipated that in the near future clinical trials with Hsp90 inhibitors will be initiated also for oesophageal cancer, using the experience from other trials.Keywords
This publication has 87 references indexed in Scilit:
- Hsp90 inhibitor PU-H71, a multimodal inhibitor of malignancy, induces complete responses in triple-negative breast cancer modelsProceedings of the National Academy of Sciences of the United States of America, 2009
- Hsp90 is expressed and represents a therapeutic target in human oesophageal cancer using the inhibitor 17-allylamino-17-demethoxygeldanamycinBritish Journal of Cancer, 2009
- Silencing the cochaperone CDC37 destabilizes kinase clients and sensitizes cancer cells to HSP90 inhibitorsOncogene, 2008
- Structural and functional coupling of Hsp90- and Sgt1-centred multi-protein complexesThe EMBO Journal, 2008
- P-Glycoprotein–Mediated Resistance to Hsp90-Directed Therapy Is Eclipsed by the Heat Shock ResponseCancer Research, 2008
- Critical regulation of TGFβ signaling by Hsp90Proceedings of the National Academy of Sciences of the United States of America, 2008
- Src-mediated Phosphorylation of Hsp90 in Response to Vascular Endothelial Growth Factor (VEGF) Is Required for VEGF Receptor-2 Signaling to Endothelial NO SynthaseMolecular Biology of the Cell, 2007
- A small molecule cell-impermeant Hsp90 antagonist inhibits tumor cell motility and invasionOncogene, 2007
- An Acetylation Site in the Middle Domain of Hsp90 Regulates Chaperone FunctionMolecular Cell, 2007
- Development of 17-allylamino-17-demethoxygeldanamycin hydroquinone hydrochloride (IPI-504), an anti-cancer agent directed against Hsp90Proceedings of the National Academy of Sciences of the United States of America, 2006