摘要
背景:靶向药物调节选择性通路激活或仅在癌细胞中被抑制,从而导致更严重的对化疗的反应和不太严重的副作用。一个选定的热休克蛋白70(HSP70)家族的使用在治疗结直肠癌的有效治疗靶点(CRC)是这篇评论的焦点。 方法:我们针对这项研究提出了两个主要的问题:1)什么是目前和潜在的未来的分子治疗在结直肠癌?2)HSP70家族的药物设计和药物发现可用于结直肠癌患者的治疗吗?我们根据他们的意义翻译现有的文献讨论了相关的文章。 结果:本次调查的第一部分讨论了分子靶向药物,目前在临床上成功地用于治疗与结肠癌患者,并强调了一些新的有针对性的药物正在进行的试验研究。这篇评论的第二部分着重对热休克蛋白,独特的致肿瘤性的功能,特别是mortalin-2,在正常细胞中线粒体的生物合成和结肠癌细胞的主要蛋白必不可少的热休克蛋白。基础和临床研究已经证实mortalin-2作为一个潜在的分子靶点,其抑制作用能显著提高患者对标准治疗反应。 结论:在分子水平上对HSP70家族成员的CRC的贡献进一步的了解,结合新理念转化为有效的靶向治疗的翻译,预计改善临床预后与细胞毒性药物联合治疗提高治疗的协同作用。
关键词: 热休克蛋白,mortalin-2,结肠癌,凋亡,靶向治疗,化疗。
Current Medicinal Chemistry
Title:Heat Shock Protein 70s as Potential Molecular Targets for Colon Cancer Therapeutics
Volume: 23 Issue: 28
Author(s): Jennifer D. Black, Khosrow Rezvani
Affiliation:
关键词: 热休克蛋白,mortalin-2,结肠癌,凋亡,靶向治疗,化疗。
摘要: Background: Targeted drugs modulate selective pathways activated or repressed only in cancer cells, resulting in a higher response to chemotherapy with less severe side effects. The use of a selected member of the heat shock protein 70 family (HSP70) as an effective therapeutic target in the treatment of colorectal cancer (CRC) will be the focus of this review.
Methods: We generated two main questions for this study: 1) What are the current and potential future molecular therapies in CRC? 2) Can selective members of the HSP70 family advance drug design and drug discovery for treatment of CRC patients? We discuss related articles based on their significance and translational contributions to the existing literature.
Results: The first part of this review discusses molecularly targeted agents that are currently used successfully in the clinic for the treatment of patients with CRC and highlights several novel targeted agents that are being investigated in ongoing trials. The second part of this review focuses on the unique tumorigenic functions of heat shock proteins, particularly mortalin-2, an essential heat shock protein for mitochondrial biogenesis in normal cells and a dominant oncoprotein in colon cancer cells. Basic and clinical studies have justified mortalin-2 as a potential molecular target, and its inhibition could dramatically improve patients’ responses to standard chemotherapies.
Conclusion: Further understanding of the contributions of HSP70 family members to CRC at the molecular level, combined with translation of new concepts into effective targeted therapies, are anticipated to improve clinical outcomes and increase the therapeutic synergy with combination treatment with cytotoxic agents.
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Cite this article as:
Jennifer D. Black, Khosrow Rezvani , Heat Shock Protein 70s as Potential Molecular Targets for Colon Cancer Therapeutics, Current Medicinal Chemistry 2016; 23 (28) . https://dx.doi.org/10.2174/0929867323666160627105033
DOI https://dx.doi.org/10.2174/0929867323666160627105033 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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