Current Status and Future Perspectives of PI3K and mTOR Inhibitor as Anticancer Drugs in Breast Cancer

Xiaobei      Zhang; Xi-ru      Li; Jin      Zhang

doi:10.2174/1568009611313020007

Abstract

The PI3K/Akt/mTOR signaling pathway is involved in the inhibition of tumor cell apoptosis, the promotion of cell survival, cell cycle regulation, tumor angiogenesis, invasion, and metastasis and therefore plays an important role in tumorigenesis, tumor growth, patient prognosis, and tumor treatment. Recent studies have identified this signaling pathway in breast cancer, and the PI3K/Akt/mTOR pathway is therefore being considered as a new therapeutic target and a hotspot in breast cancer research. Pre-clinical studies have confirmed that PI3K inhibitors and mTOR inhibitors achieve anticancer effects by targeting different levels of the PI3K/Akt/mTOR signaling pathway. Among the PI3K inhibitors, some molecules target only PI3K, whereas others target both PI3K and mTOR. Currently, researchers tend to focus on molecular targets based on the different PI3K subtypes to achieve more targeted and specific inhibition of the PI3K pathway. However, the clinical efficacy and efficiency of these inhibitors need to be further studied. The mTOR inhibitors target mTORC1 and have become relatively well-developed targeted therapies for the PI3K/AKT/mTOR pathway. Rapamycin derivatives have been studied in Phase II / III clinical trials in breast cancer, and these derivatives achieved positive results in the treatment of metastatic breast cancer when combined with endocrine therapy or HER2-targeted therapies. This review summarizes the activation of the PI3K/AKT/mTOR pathway, its role in breast cancer, and the latest clinical trials of a variety of PI3K and mTOR inhibitors to improve the understanding of the role of these drugs in breast cancer treatment.

Keywords: Breast cancer, mTOR inhibitors, PI3K/AKT/mTOR pathway, PI3K inhibitors.

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