Oncogenic PI3KT/Akt/mTOR Pathway Alterations, ROS Homeostasis, Targeted Cancer therapy and drug resistance

The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is an important signaling route that regulates several cell functions. PI3K/AKT/mTOR pathway is a crossroad of cell death and survival, playing a pivotal role in multiple interconnected cell signaling mechanisms implicated in cell metabolism, growth and proliferation, apoptosis, and angiogenesis. Disruptions in the Akt‑regulated pathways and alterations in PTEN expression are associated to Reactive oxygen species (ROS) homeostasis and different types of cancer. Genomic studies have shown that activating mutations in oncogenes as well as inactivating mutations in tumor suppressor genes are present across a variety of malignancies, including constitutive activation of the PI3K/AKT/mTOR pathway. The regulation of the Akt signaling pathway renders multiple challenges and valuable therapeutic targets. The discovery process of Akt, PDK1 and mTOR synthetic and natural products as inhibitors or immune checkpoint inhibitors using various strategies, could led to the identification of small molecule inhibitors with great selectivity, low side‑effects and also low toxicity regarding drug development.

The scope of this research topic covers the studies offering original research articles; systematic reviews; clinical trials on:

• PI3K/AKT/mTOR pathway in cancer genesis

• PI3K inhibition as a potential strategy to develop novel therapeutics for cancer

• Activation of mTOR, tumor growth, metastasis and mTOR inhibitors development

to treatment of cancer

• Meta-analysis to explore the clinical significance of PI3K/AKT/mTOR inhibitor

• Meta-analysis to explore AKT and mTOR expression in patients with different kinds

of tumor

• Natural herbals and PI3K/AKT/mTOR modulation

• ROS module PI3K/AKT/mTOR pathway and cancer initiation and progression

• Activation of AKT, a key protein in PI3K/Akt signaling pathway, a prognostic role

in various hematologic and solid tumors

• Mutations in AKT1 and alterations in PTEN promoting cell survival

• Alteration in the PIK3CA-AKT1-PTEN pathway and cancer prevalence

• PI3K/AKT/mTOR pathway inhibitor and the risk of adverse effects and drug

resistance

Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.