PI3K/AKT/MTOR: CONTRIBUTION TO THE TUMOR PHENOTYPE SENSITIVE TO TAMOXIFEN

Abstract

The PI3K/Akt/mTOR is a key signaling system that binds oncogenes and various receptors to many cell functions, promotes estrogen resistance, and is the most frequently activated signaling pathway in malignant neoplasm, including breast cancer (BC). About 70 % of BC is hormone‑receptor positive and the endocrine therapy is the main component of treatment for hormone‑receptor positive BC patients. Tamoxifen remains one of the basic drugs for adjuvant endocrine therapy in estrogen‑positive BC patients. However, due to acquired resistance to this drug, 25–30 % of patients develop a relapse or disease progression. Resistance to tamoxifen is one of the key clinical problems in the treatment of estrogen‑positive BC. The potential mechanisms of tamoxifen resistance may be associated with crosstalk between estrogen receptors and PI3K/Akt/mTOR signaling. This review summarizes the current literature data on the role of the PI3K/Akt/mTOR signaling pathway in the mechanisms of hormonal resistance, including a complete characterization of its main components and the features of PI3K/Akt/mTOR interaction with estrogen receptors. The results of studies of the main components of the cascade as molecular markers of response to tamoxifen therapy in estrogen‑positive BC patients are presented. Further study of the PI3K/Akt/mTOR crosstalk with various signaling pathways will contribute to both the understanding of carcino‑ genesis and the development of new molecular‑targeted anticancer drugs for the treatment of tamoxifen‑ resistant breast tumors.