Strategic advancements in targeting the PI3K/AKT/mTOR pathway for Breast cancer therapy.

Biochem Pharmacol

Department of Medical Oncology & Therapeutics Research, Beckman Research Institute of City of Hope, Comprehensive Cancer Center and National Medical Center, Duarte, CA 91010, USA. Electronic address:

Published: March 2025

Breast cancer (BC) is a complex disease that affects millions of women worldwide. Its growing impact calls for advanced treatment strategies to improve patient outcomes. The PI3K/AKT/mTOR pathway is a key focus in BC therapy because it plays a major role in important processes like tumor growth, survival, and resistance to treatment. Targeting this pathway could lead to better treatment options and outcomes. The present review explores how the PI3K/AKT/mTOR pathway becomes dysregulated in BC, focusing on the genetic changes like PIK3CA mutations and PTEN loss that leads to its aggravation. Current treatment options include the use of inhibitors targeting PI3K, AKT, and mTOR with combination therapies showing promise in overcoming drug resistance and improving effectiveness. Looking ahead, next-generation inhibitors and personalized treatment plans guided by biomarker analysis may provide more accurate and effective options for patients. Integrating these pathway inhibitors with immunotherapy offers an exciting opportunity to boost anti-tumor responses and improve survival rates. This review offers a comprehensive summary of the current progress in targeting the PI3K/AKT/mTOR pathway in BC. It highlights future research directions and therapeutic strategies aimed at enhancing patient outcomes and quality of life.

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http://dx.doi.org/10.1016/j.bcp.2025.116850DOI Listing

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