Uppsala University, Deparment of Oncology, Radiology and Clinical Immunology, Unit of Oncology, SE-751 85 Uppsala, Sweden.
Expert Opin Ther Targets. 2010 Mar;14(3):317-28. doi: 10.1517/14728221003621278.
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.
食管癌的预后很差，5 年总生存率仅为 10-20%。该疾病通常在晚期诊断，此时可能已经发生了扩散，导致预后不良。然而，靶向治疗的最新进展为治疗手段提供了新的可能。热休克蛋白 90（Hsp90）已被证明可保护信号分子的致癌变异体免于降解，从而促进细胞生长和存活。已发现 Hsp90在食管癌中大量表达，可能成为治疗这种疾病的治疗靶点。
我们总结了有关 Hsp90 在食管癌中的作用的现有数据，以及其他肿瘤类型的可用信息。
能够详细阐述 Hsp90 的作用机制，并讨论涉及 HSP90 抑制剂在恶性肿瘤中的临床试验的最新进展，特别强调食管癌。
食管癌中 Hsp90 抑制的临床前研究很有希望，预计不久的将来，将根据其他试验的经验，为食管癌启动 HSP90 抑制剂的临床试验。
