Genetic Interactions of STAT3 and Anticancer Drug Development.
Genetic Interactions of STAT3 and Anticancer Drug Development.
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STAT3和抗癌药物开发的遗传相互作用。
DOI：
10.3390/cancers6010494
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发表时间：
2014-03-06
期刊：
影响因子：
5.2
通讯作者：
Fang B
中科院分区：
文献类型：
--
作者：
Fang B
信号转导子和转录激活子3（STAT 3）在肿瘤的发生和恶性进展中起着重要作用，并已被广泛研究作为肿瘤治疗的靶点。已经在实验肿瘤模型中评估了许多STAT 3抑制剂的体外和体内抗肿瘤活性，并且已经报道了几种批准的治疗剂作为STAT 3抑制剂起作用。然而，大多数STAT 3抑制剂尚未转化为癌症治疗的临床评估，可能是因为药代动力学，疗效和安全性问题。事实上，抗癌药物开发失败的一个主要原因是缺乏疗效。各种癌症相关途径之间的遗传相互作用通常提供来自平行和/或合作途径的冗余输入，这些途径驱动并维持癌细胞的存活环境，导致单靶点药物的低疗效。利用STAT 3与其他癌症相关通路的遗传相互作用可以提供对癌症对通路靶向治疗的耐药性机制的分子见解，以及开发更有效的抗癌药物和治疗方案的策略。本文综述了STAT 3活性的功能调节; STAT 3、RAS、表皮生长因子受体和还原-氧化途径之间可能的相互作用;以及调节STAT 3抑制剂治疗效果的分子机制。
Signal transducer and activator of transcription 3 (STAT3) plays critical roles in tumorigenesis and malignant evolution and has been intensively studied as a therapeutic target for cancer. A number of STAT3 inhibitors have been evaluated for their antitumor activity in vitro and in vivo in experimental tumor models and several approved therapeutic agents have been reported to function as STAT3 inhibitors. Nevertheless, most STAT3 inhibitors have yet to be translated to clinical evaluation for cancer treatment, presumably because of pharmacokinetic, efficacy, and safety issues. In fact, a major cause of failure of anticancer drug development is lack of efficacy. Genetic interactions among various cancer-related pathways often provide redundant input from parallel and/or cooperative pathways that drives and maintains survival environments for cancer cells, leading to low efficacy of single-target agents. Exploiting genetic interactions of STAT3 with other cancer-related pathways may provide molecular insight into mechanisms of cancer resistance to pathway-targeted therapies and strategies for development of more effective anticancer agents and treatment regimens. This review focuses on functional regulation of STAT3 activity; possible interactions of the STAT3, RAS, epidermal growth factor receptor, and reduction-oxidation pathways; and molecular mechanisms that modulate therapeutic efficacies of STAT3 inhibitors.
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影响因子：
7.3
作者：
Astsaturov I;Ratushny V;Sukhanova A;Einarson MB;Bagnyukova T;Zhou Y;Devarajan K;Silverman JS;Tikhmyanova N;Skobeleva N;Pecherskaya A;Nasto RE;Sharma C;Jablonski SA;Serebriiskii IG;Weiner LM;Golemis EA
通讯作者：
Golemis EA
影响因子：
10.5
作者：
Ancrile, Brooke;Lim, Kian-Huat;Counter, Christopher M.
通讯作者：
Counter, Christopher M.
DOI：
10.1073/pnas.171302098
发表时间：
2001-08-14
影响因子：
11.1
作者：
Betz, A;Lampen, N;Darnell, JE
通讯作者：
Darnell, JE
影响因子：
168.9
作者：
Aponte, John J.;Schellenberg, David;Menendez, Clara
通讯作者：
Menendez, Clara
影响因子：
64.5
作者：
BUDAY, L;DOWNWARD, J
通讯作者：
DOWNWARD, J