Emerging therapeutics for targeting Akt in cancer
Emerging therapeutics for targeting Akt in cancer
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DOI：
10.2741/4419
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发表时间：
2016-01-01
影响因子：
3.1
通讯作者：
Basu, Alakananda
中科院分区：
文献类型：
--
作者：
Gdowski, Andrew;Panchoo, Marlyn;Basu, Alakananda
癌症治疗研究的最终目标是开发有效的、有针对性的疗法，利用癌细胞的脆弱性。Akt的三种同种型，也称为蛋白激酶B（PKB），是将促有丝分裂信号从细胞外部传递到细胞内部的效应蛋白的各种途径的重要介质。由于Akt在细胞功能如生长、增殖和细胞存活中的重要性，许多癌细胞依赖于该途径来帮助它们存活。这种依赖性可导致化学抗性和选择更适应的癌细胞群体。因此，了解亚型特异性的功能意义及其与化疗耐药性的关系是很重要的。本文综述了Akt亚型的特异性调控及其在化疗耐药中的作用，强调了Akt亚型作为肿瘤治疗靶点的潜力。我们还浓缩了正在进行的涉及各种类型Akt抑制剂的临床研究，同时强调了将Akt亚型鉴定为有希望的治疗靶点所涉及的研究类型、原理和联合治疗。
The ultimate goal of cancer therapeutic research is to develop effective, targeted therapeutics that exploit the vulnerabilities of cancer cells. The three isoforms of Akt, also known as protein kinase B (PKB), are important mediators of various pathways that transmit mitogenic signals from the cell's exterior to the effector proteins of the cell's interior. Due to Akt's importance in cell functions such as growth, proliferation and cell survival, many cancer cells rely on this pathway to aid in their survival. This dependence can lead to chemoresistance and selection of more adapted populations of cancer cells. Thus, it is important to understand the functional significance of isoform specificity and its relation to chemoresistance. In this review, we have summarized recent studies on Akt isoform specific regulation as well as each isoform's role in chemoresistance, emphasizing their potential as targets for cancer therapy. We have also condensed ongoing clinical studies involving various types of Akt inhibitors while highlighting the type of study, rationale and co-therapies involved in identifying Akt isoforms as promising therapeutic targets.