Biomarkers-guided precision therapeutics has revolutionized the clinical development and administration of molecular-targeted anticancer agents. Tailored precision cancer therapy exhibits better response rate compared to unselective treatment. Protein kinases have critical roles in cell signaling, metabolism, proliferation, survival and migration. Aberrant activation of protein kinases is critical for tumor growth and progression. Hence, protein kinases are key targets for molecular targeted cancer therapy. The serine/threonine kinase Akt is frequently activated in various types of cancer. Activation of Akt promotes tumor progression and drug resistance. Since the first Akt inhibitor was reported in 2000, many Akt inhibitors have been developed and evaluated in either early or late stage of clinical trials, which take advantage of liquid biopsy and genomic or molecular profiling to realize personalized cancer therapy. Two inhibitors, capivasertib and ipatasertib, are being tested in phase III clinical trials for cancer therapy. Here, we highlight recent progress of Akt signaling pathway, review the up-to-date data from clinical studies of Akt inhibitors and discuss the potential biomarkers that may help personalized treatment of cancer with Akt inhibitors. In addition, we also discuss how Akt may confer the vulnerability of cancer cells to some kinds of anticancer agents.

中文翻译：

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靶向癌症中的 Akt 进行精准治疗

生物标志物引导的精准治疗彻底改变了分子靶向抗癌药物的临床开发和管理。与非选择性治疗相比，量身定制的精准癌症治疗显示出更好的反应率。蛋白激酶在细胞信号、代谢、增殖、存活和迁移中具有关键作用。蛋白激酶的异常激活对肿瘤生长和进展至关重要。因此，蛋白激酶是分子靶向癌症治疗的关键目标。丝氨酸/苏氨酸激酶 Akt 在各种类型的癌症中经常被激活。Akt 的激活促进肿瘤进展和耐药性。自 2000 年第一个 Akt 抑制剂被报道以来，许多 Akt 抑制剂已经在临床试验的早期或后期阶段被开发和评估，利用液体活检和基因组或分子分析实现个性化癌症治疗。两种抑制剂 capivasertib 和 ipatasertib 正在癌症治疗的 III 期临床试验中进行测试。在这里，我们重点介绍了 Akt 信号通路的最新进展，回顾了 Akt 抑制剂临床研究的最新数据，并讨论了可能有助于使用 Akt 抑制剂个性化治疗癌症的潜在生物标志物。此外，我们还讨论了 Akt 如何赋予癌细胞对某些抗癌药物的脆弱性。回顾 Akt 抑制剂临床研究的最新数据，并讨论可能有助于 Akt 抑制剂个性化治疗癌症的潜在生物标志物。此外，我们还讨论了 Akt 如何赋予癌细胞对某些抗癌药物的脆弱性。回顾 Akt 抑制剂临床研究的最新数据，并讨论可能有助于 Akt 抑制剂个性化治疗癌症的潜在生物标志物。此外，我们还讨论了 Akt 如何赋予癌细胞对某些抗癌药物的脆弱性。