New Treatment Opportunities in Phosphatase and Tensin Homolog (PTEN)-Deficient Tumors: Focus on PTEN/Focal Adhesion Kinase Pathway.
New Treatment Opportunities in Phosphatase and Tensin Homolog (PTEN)-Deficient Tumors: Focus on PTEN/Focal Adhesion Kinase Pathway.
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DOI：
10.3389/fonc.2017.00170
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发表时间：
2017
影响因子：
4.7
通讯作者：
Cavazzoni A
中科院分区：
文献类型：
--
作者：
Alfieri R;Giovannetti E;Bonelli M;Cavazzoni A
深入的遗传学研究表明，磷酸酶和张力蛋白同源物（PTEN）突变或表达缺失不是癌症发展的早期事件，而是肿瘤进展和侵袭的特征。PTEN功能的丧失导致促生存磷脂酰肌醇3-激酶（PI 3 K）/AKT/mTOR通路的完全激活，但是用PI 3 K/AKT/mTOR的特异性抑制剂的治疗没有产生预期的结果。PTEN的替代靶点之一是粘着斑激酶（FAK）激酶，其主要参与控制癌细胞扩散。PTEN和FAK之间的联系已在不同的肿瘤类型中得到证实，其中PTEN活性降低通常与FAK的表达和磷酸化增加相关。因此，FAK抑制可能代表一种有前途的策略，一些临床试验正在测试FAK抑制剂单独或与其他药物联合用于许多实体瘤。然而，只有很少的临床前和临床数据描述了PI 3 K/AKT/mTOR和FAK抑制剂组合的作用。增加对PTEN/FAK连接的了解可以证实，在具有改变或降低的PTEN表达的晚期转移性恶性肿瘤中，PTEN作为基于PI 3 K/AKT和FAK信号传导的伴随抑制的组合策略的良好预后标志物。
Deep genetic studies revealed that phosphatase and tensin homolog (PTEN) mutations or loss of expression are not early events in cancer development but characterize tumor progression and invasion. Loss of PTEN function causes a full activation of the prosurvival phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway, but the treatment with specific inhibitors of PI3K/AKT/mTOR did not produce the expected results. One of the alternative targets of PTEN is the focal adhesion kinase (FAK) kinase, mainly involved in the control of cancer cell spread. The connection between PTEN and FAK has been demonstrated in different tumor types, with reduced PTEN activity often correlated with increased expression and phosphorylation of FAK. FAK inhibition may thus represent a promising strategy, and some clinical trials are testing FAK inhibitors alone or combined with other agents in a number of solid tumors. However, only few preclinical and clinical data described the effects of the combination of PI3K/AKT/mTOR and FAK inhibitors. Increasing knowledge on the PTEN/FAK connection could confirm PTEN as a good prognostic marker for a combination strategy based on concomitant inhibition of PI3K/AKT and FAK signaling, in advanced metastatic malignancies with altered or reduced PTEN expression.
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影响因子：
64.8
作者：
通讯作者：
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DOI：
10.1158/1078-0432.ccr-13-1638
发表时间：
2014-02-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Cumberbatch M;Tang X;Beran G;Eckersley S;Wang X;Ellston RP;Dearden S;Cosulich S;Smith PD;Behrens C;Kim ES;Su X;Fan S;Gray N;Blowers DP;Wistuba II;Womack C
通讯作者：
Womack C
影响因子：
--
作者：
Cui, Lei;Li, Yuejun;Li, Xueyong
通讯作者：
Li, Xueyong
影响因子：
50.5
作者：
Gonzalez-Angulo, A. M.;Akcakanat, A.;Meric-Bernstam, F.
通讯作者：
Meric-Bernstam, F.
影响因子：
6.6
作者：
Haber, Tobias;Joeckel, Elke;Brenner, Walburgis
通讯作者：
Brenner, Walburgis