PI3K/AKT/mTOR Axis in Cancer: From Pathogenesis to Treatment

Area of Science:

• Oncology
• Molecular Biology
• Cell Signaling

Background:

• The PI3K/AKT/mTOR signaling axis controls fundamental cellular processes like proliferation, metabolism, and survival.
• Dysregulation of this pathway is a key driver of cancer development, progression, and resistance to therapies.
• A comprehensive understanding of the PI3K/AKT/mTOR pathway's multifaceted roles in cancer is still evolving.

Purpose of the Study:

• To provide an integrated review of the PI3K/AKT/mTOR pathway's oncogenic mechanisms.
• To explore its regulation of critical cellular processes and its role in therapeutic resistance.
• To evaluate emerging therapeutic strategies targeting this pathway for precision oncology.

Main Methods:

• Comprehensive literature review of the PI3K/AKT/mTOR pathway in cancer biology and therapeutics.
• Analysis of oncogenic mechanisms including EMT, autophagy, apoptosis, and metabolic reprogramming.
• Evaluation of epigenetic regulation by noncoding RNAs and pathway's impact on treatment response.

Main Results:

• The PI3K/AKT/mTOR pathway governs tumor hallmarks, including epithelial-mesenchymal transition, autophagy, apoptosis, and metabolic shifts (glycolysis, ferroptosis, lipid metabolism).
• Autophagy plays a dual role, influencing therapeutic resistance and cancer dynamics.
• Epigenetic regulators (miRNAs, lncRNAs, circRNAs) and the pathway's interplay with chemotherapy, radiotherapy, and immunotherapy are significant.
• The pathway significantly impacts the tumor microenvironment and treatment outcomes.

Conclusions:

• The PI3K/AKT/mTOR pathway is a central therapeutic target in oncology.
• Targeting this axis offers potential for precision oncology approaches to enhance treatment efficacy and overcome resistance.
• Further research into integrated strategies is crucial for improving cancer patient outcomes.