Cancer Molecular Pathology, School of Medicine, Griffith University, Gold Coast, Australia.
Histol Histopathol. 2019 Jun;34(6):593-609. doi: 10.14670/HH-18-081. Epub 2019 Jan 8.
The vital need for Akt in maintaining basic cellular function has highlighted its importance in carcinogenesis. Unfortunately, Akt inhibitor development outcome has remained poor, as most of them have failed to show significant clinical benefit to cancer patients during the clinical trials. Recently, a new class of non-coding RNAs, known as long non-coding RNAs (lncRNAs), which show high tissue specificity, have demonstrated great influence in cancer progression and/or cancer inhibition. As both Akt signalling pathways and lncRNAs play such innate roles in carcinogenesis, identifying the specific roles that these lncRNAs play within this pathway may represent a novel research avenue for developing Akt inhibitors with better therapeutic properties. In addition, understanding the diverse mechanism by which lncRNAs regulate gene expression can assist in deciphering the fundamentals of carcinogenesis. The focus of interest should be on the lncRNAs, which affect Akt and finding the link between lncRNAs and Akt pathways associated with carcinogenesis. LncRNAs within the Akt pathways could affect multiple pathways in a particular cancer type, which ultimately creates an intricate web of connections between the pathways. In summary, lncRNAs have tremendous potential in cancer diagnosis, assessing cancer patient prognosis and in developing new therapeutic options for patients with resistance to current cancer therapies. Thus, understanding how lncRNAs influence the Akt pathway is essential for the development of novel and effective cancer therapies.
在维持基本细胞功能方面，Akt 的至关重要性凸显了其在致癌作用中的重要性。不幸的是， Akt 抑制剂的开发结果仍然不佳，因为在临床试验中，它们中的大多数未能为癌症患者带来显著的临床获益。最近，一类新的非编码 RNA，即长非编码 RNA（lncRNA），由于具有高度的组织特异性，在癌症进展和/或癌症抑制方面表现出了巨大的影响。由于 Akt 信号通路和 lncRNA 都在致癌作用中发挥着这种固有作用，因此确定这些 lncRNA 在该通路中所扮演的特定角色可能代表着开发具有更好治疗特性的 Akt 抑制剂的一个新的研究途径。此外，了解 lncRNA 调节基因表达的不同机制有助于解析致癌作用的基本原理。关注的焦点应该是那些影响 Akt 的 lncRNA，并找到与致癌作用相关的 lncRNA 和 Akt 通路之间的联系。Akt 通路中的 lncRNA 可能会影响特定癌症类型中的多个通路，这最终会在通路之间形成一个错综复杂的连接网络。总之，lncRNA 在癌症诊断、评估癌症患者预后以及为对现有癌症疗法产生耐药性的患者开发新的治疗选择方面具有巨大的潜力。因此，了解 lncRNA 如何影响 Akt 通路对于开发新的有效的癌症疗法至关重要。
