摘要
Hedgehog (Hh)信号传导在一些血液和固体癌症被异常激活。可选择的治疗在泌尿系统癌症中经常缺乏,因为它们的发展机制几乎就不被知道。建立抗肿瘤效果和安全的Hh通路的抑制剂用于Hh通路被激活的癌症的研究总是需要的。当前,vismodegib是临床上有效的用于基底细胞癌治疗,并且预期能够扩展用于其他癌症治疗。维生素D3是活性维生素D3的前体物质,它是一个强效的Shh-Gli信号传导抑制剂并且在肾癌中可能具有生长抑制作用。作为一个补充的治疗药物其有可能促进肿瘤的消退。前列腺癌的临床前数据显示,压制Hh信号传导能够降低肿瘤侵润和转移,在长期使用后它也能导致药物获得性抵抗。联合Hh抑制剂和离子化辐射和/或化疗能够改善治疗,同时减低获得性耐药的风险。Shh相关的配体基因的表达和Shh-Gli诱导的靶向基因如FOXM1或IGF2是泌尿系统肿瘤样本的特征。在96%的非肌肉侵润性膀胱癌和52%的肌肉浸润性膀胱癌样本中都观察到Shh的过度表达。本综述概括了近期报道的Hh信号传导激活在泌尿系统癌症中的研究趋势,尤其注重在临床上应用的可能性。
关键词: Hedgehog信号传导,泌尿系统癌症
Current Drug Targets
Title:Hedgehog Signaling and Urological Cancers
Volume: 16 Issue: 3
Author(s): Katsumi Shigemura and Masato Fujisawa
Affiliation:
关键词: Hedgehog信号传导,泌尿系统癌症
摘要: Hedgehog (Hh) signaling is aberrantly activated in several hematological and solid cancers. Therapeutic options are sometimes lacking for urological cancers because their mechanisms of progression are imperfectly understood. Studies establishing the anti-tumor effects and safety of inhibitors of Hh pathways are needed for tumors in which the Hh pathways are activated. At present vismodegib is clinically available for basal cell carcinoma, and is expected to be extended to treat other cancers. Cholecalciferol, the precursor of active vitamin D3, is a strong inhibitor of Shh-Gli signaling and may have growth inhibitory effects in renal cancer. As a supplementary therapy it may promote tumor regression. Preclinical data in prostate cancer suggest that while suppressing Hh signaling could reduce invasion and metastasis, it may also result in acquired drug resistance after long-term use. Combining Hh inhibitors with ionizing radiation and/or chemotherapy could improve treatment while lessening the risk of acquired drug resistance. Expression of Shhrelated ligand gene and Shh-Gli-inducible target genes like FOXM1 or IGF2 is characteristic of urothelial tumor samples. Overexpression of Shh is observed in 96% of non-muscle invasive bladder cancer and 52% of muscle invasive bladder cancer samples. This review summarizes recently reported trends in Hh signaling activation studies in urological cancer, especially focusing on possible clinical applications.
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Cite this article as:
Katsumi Shigemura and Masato Fujisawa , Hedgehog Signaling and Urological Cancers, Current Drug Targets 2015; 16 (3) . https://dx.doi.org/10.2174/1389450115666141125122643
DOI https://dx.doi.org/10.2174/1389450115666141125122643 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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