Programs in Biochemistry and Cancer Biology, and Departments of Molecular and Medical Genetics, University of North Texas Health Science Center and Institute for Cancer Research, Fort Worth, Texas, 76107.
Programs in Biochemistry and Cancer Biology, and Departments of Molecular and Medical Genetics, University of North Texas Health Science Center and Institute for Cancer Research, Fort Worth, Texas, 76107,
Front Biosci (Landmark Ed). 2016 Jan 1;21(4):757-68. doi: 10.2741/4419.
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.
癌症治疗研究的最终目标是开发有效、靶向的治疗方法，利用癌细胞的脆弱性。Akt 的三种同工型，也称为蛋白激酶 B（PKB），是从细胞外部传递有丝分裂信号到细胞内部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、增殖和细胞存活中非常重要，许多癌细胞依赖这条途径来帮助它们存活。这种依赖性可能导致化疗耐药性和更适应的癌细胞群体的选择。因此，了解同工型特异性的功能意义及其与化疗耐药性的关系非常重要。在这篇综述中，我们总结了最近关于 Akt 同工型特异性调节以及每种同工型在化疗耐药性中的作用的研究，强调了它们作为癌症治疗靶点的潜力。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，同时强调了作为有前途的治疗靶点确定 Akt 同工型的研究类型、基本原理和联合治疗。
