Arunaksharan Narayanankutty* Pages 188 - 199 ( 12 )
Background: Breast cancer is the predominant form of cancer in women; various cellular pathways are involved in the initiation and progression of breast cancer. Among the various types of breast cancer that differ in their growth factor receptor status, PI3K/Akt signaling is a common pathway where all these converge. Thus, the PI3K signaling is of great interest as a target for breast cancer prevention; however, it is less explored.Objective: The present review is aimed to provide a concise outline of the role of PI3K/Akt/mTOR pathway in breast carcinogenesis and its progression events, including metastasis, drug resistance and stemness. The review emphasizes the role of natural and synthetic inhibitors of PI3K/Akt/m- TOR pathway in breast cancer prevention. Methods: The data were obtained from PubMed/Medline databases, Scopus and Google patent literature. Results: PI3K/Akt/mTOR signaling plays an important role in human breast carcinogenesis; it acts on the initiation and progression events associated with it. Numerous molecules have been isolated and identified as promising drug candidates by targeting the signaling pathway. Results from clinical studies confirm their application in the treatment of human breast cancer alone and in combination with classical chemotherapeutics as well as monoclonal antibodies. Conclusion: PI3K/mTOR signaling blockers have evolved as promising anticancer agents by interfering breast cancer development and progression at various stages. Natural products and bioactive components are emerging as novel inhibitors of PI3K signaling and more research in this area may yield numerous drug candidates.
Breast cancer, carcinogenesis, curcumin, drug development, metastasis, natural products, PI3K/Akt/mTOR pathway.
Division of Cell and Molecular Biology, Post Graduate & Research Department of Zoology, St. Joseph’s College (Autonomous), Devagiri, Kerala