Emerging strategies for EphA2 receptor targeting for cancer therapeutics.
Emerging strategies for EphA2 receptor targeting for cancer therapeutics.
复制标题
DOI：
10.1517/14728222.2011.538682
复制
发表时间：
2011-01
影响因子：
5.8
通讯作者：
Mittal SK
中科院分区：
文献类型：
--
作者：
Tandon M;Vemula SV;Mittal SK
癌症的高死亡率要求进一步发展早期诊断和更好的治疗策略。膜结合肝细胞受体酪氨酸激酶A2类（EphA2）在乳腺癌、前列腺癌、膀胱癌、皮肤癌、肺癌、卵巢癌和脑癌中过度表达。本文综述了EphA2在癌症中的过表达、信号机制和调控策略。EphA2在癌细胞中的高表达与预后不良相关，并与转移增强导致的复发相关。EphA2受体与其配体（如EphrinA1）的相互作用引发了一些不受调控的事件，并与致癌有关。描述了EphA2不依赖ephrina1的致癌活性和依赖ephrina1的抑瘤作用。EphA2与信号蛋白的分子相互作用与细胞骨架动力学、细胞粘附、增殖、分化和转移的调节有关。EphA2信号的解除调控及其在肿瘤发生中的作用为合理设计干预方法提供了多种途径。EphA2作为药物靶点已被多种方法测试，如激动剂抗体、RNA干扰、免疫疗法、病毒载体介导的基因转移、小分子抑制剂和纳米颗粒。经过十多年的研究，EphA2在各种临床前癌症模型中成功靶向表达的令人鼓舞的结果需要进一步的研究。
High mortality rates with cancers warrant further development of earlier diagnostics and better treatment strategies. Membrane-bound hepatocellular receptor tyrosine kinase class A2 (EphA2) is overexpressed in breast, prostate, urinary bladder, skin, lung, ovary and brain cancers. This review describes EphA2 overexpression in cancers, its signaling mechanisms and strategies to target its deregulation. High EphA2 expression in cancer cells is correlated to a poor prognosis associated with recurrence due to enhanced metastasis. Interaction of the EphA2 receptor with its ligand (e.g., EphrinA1) triggers events that are deregulated and implicated in carcinogenesis. Both EphrinA1-independent oncogenic activity and EphrinA1-dependent tumor suppressor roles for EphA2 are described. Molecular interactions of EphA2 with signaling proteins are associated with the modulation of cytoskeleton dynamics, cell adhesion, proliferation, differentiation and metastasis. The deregulated signaling by EphA2 and its involvement in oncogenesis provide multiple avenues for the rational design of intervention approaches. EphA2 has been tested as a drug target using multiple approaches such as agonist antibodies, RNA interference, immunotherapy, virus vectors-mediated gene transfer, small molecule inhibitors and nanoparticles. With over a decade of research, encouraging results with successful targeting of EphA2 expression in various pre-clinical cancer models necessitate further studies.
登录
查看更多内容
影响因子：
3.8
作者：
Dickerson EB;Blackburn WH;Smith MH;Kapa LB;Lyon LA;McDonald JF
通讯作者：
McDonald JF
影响因子：
11.5
作者：
Brannan, Jennifer M.;Dong, Wenli;Johnson, Faye M.
通讯作者：
Johnson, Faye M.
DOI：
10.1023/b:jomg.0000017433.83226.22
发表时间：
2003-10-01
影响因子：
2.5
作者：
Andres, AC;Ziemiecki, A
通讯作者：
Ziemiecki, A
影响因子：
21.3
作者：
Carter, N;Nakamoto, T;Hunter, T
通讯作者：
Hunter, T
DOI：
10.1007/s00259-007-0503-5
发表时间：
2007-12-01
影响因子：
9.1
作者：
Cai, Weibo;Ebrahimnejad, Alireza;Chen, Xiaoyuan
通讯作者：
Chen, Xiaoyuan