摘要
背景:对治疗的耐药是癌症患者生存的主要障碍,这表明迫切需要阐明化疗耐药的潜在机制。研究证明内质网(ER)应激在正常情况下使细胞存活会导致细胞死亡方面起着重要作用。具体来说,GRP 78的高表达,未折叠蛋白反应的主调节因子已被证明能诱导化疗耐药,并可作为患者预后不良的指标。 目的:评价GRP 78及其下游靶点在多种癌症中的表达,可使临床医生预测对多种常用治疗方法的耐药性。此外,探讨GRP 78调控化疗耐药的作用机制,将促进更有效的针对GRP 78的化疗策略的开发。 结果:这篇小型综述强调了GRP 78下游靶点的作用,并探讨了它们与细胞存活相关的机制。此外,GRP 78表示符之间的联系总结提供了结论和患者预后。 最后,探讨了靶向GRP78以提高治疗效果的策略。 结论:GRP 78在调控细胞存活的信号通路中具有重要作用,本文就其作为预后指标和治疗靶点的价值进行了综述。
关键词: 癌,化疗耐药,内质网应激,GRP78,未折叠蛋白反应。
图形摘要
Current Drug Targets
Title:GRP78 Influences Chemoresistance and Prognosis in Cancer
Volume: 19 Issue: 6
关键词: 癌,化疗耐药,内质网应激,GRP78,未折叠蛋白反应。
摘要: Background: Resistance to therapy is a major hindrance to patient survival in cancer, underscoring a critical need to elucidate the underlying mechanisms responsible for chemoresistance. Research has demonstrated that endoplasmic reticulum (ER) stress plays a significant role in allowing cells to survive conditions that would normally elicit cell death. Specifically, elevated expression of GRP78, the master regulator of the unfolded protein response (UPR), has been shown to induce chemoresistance and serves as a indictor of poor prognosis in patients.
Objective: Evaluating the expression of GRP78 and its downstream targets in a wide range of cancers may allow clinicians to predict resistance to a number of commonly used therapies. Moreover, understanding the mechanism(s) of action GRP78 uses to regulate chemoresistance will accelerate the development of more efficacious treatment strategies that target GRP78 to abrogate chemoresistance.
Results: This mini-review highlighted the roles of targets downstream of GRP78 and explored their mechanisms related to cellular survival. Furthermore, a summary of the connection between GRP78 expression and patient prognosis was provided. Lastly, strategies for targeting GRP78, in order to improve treatment efficacy, was explored.
Conclusions: GRP78 maintains an important role in regulating signaling pathways that control cell survival and this review draws attention to its value as a prognostic marker and therapeutic target.
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Cite this article as:
GRP78 Influences Chemoresistance and Prognosis in Cancer, Current Drug Targets 2018; 19 (6) . https://dx.doi.org/10.2174/1389450118666170615100918
DOI https://dx.doi.org/10.2174/1389450118666170615100918 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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