Research progress and development strategy of PI3K inhibitors for breast cancer treatment: A review (2016-present).

Abstract

Phosphatidylinositol 3-kinases (PI3Ks) are widely expressed in tissues and cells throughout the body and are involved in a variety of physiological processes including cell growth and metabolism. The phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of the rapamycin (mTOR) signaling pathway (PI3K/AKT/mTOR, PAM) is a promising target for the treatment of many cancer types because it is significantly linked to tumorigenesis and development. Aberrant activation of this pathway is observed in the majority of tumors, particularly in breast cancer. The development of PI3K inhibitors has received much attention in recent years. PI3K inhibitors are effective drugs for the treatment of various types of malignant tumors. The FDA has approved a few PI3K inhibitors for commercialization, and the majority of PI3K inhibitors under clinical trials are expected to conquer cancers, including breast cancer. This article discusses the link between the PAM signaling system and breast cancer, as well as the current clinical applications of PAM pathway inhibitors in the treatment of breast cancer. This work summarizes and describes the development tactics of seven types of PI3K inhibitors targeting breast cancer, including morpholine-substituted thienopyrimidines, with the goal of informing future PI3K inhibitor research.