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.