Targeting the PI3K Pathway: Advancements and Achievements in Breast Cancer Therapy.

Abstract

Breast cancer is a complex disease caused by the aberrant and unchecked proliferation of breast cells, which leads to the development of tumours. In various types of cancer, the Phosphoinositide 3- kinase/Protein kinase B (PKB, also known as Akt (PI3K/Akt) signalling pathway, is essential for controlling cell survival, metastasis, and metabolism. Currently, marketed PI3K inhibitors for treating breast cancer face several issues, including toxicity, resistance, etc. Significant efforts have been made to develop synthetic and repurposed inhibitor drugs to target PI3K, which are now being tested in clinical trials. Developed synthetic PI3K inhibitors have been reported to have better results in clinical trials in the suppression of tumors. This review article mainly focuses on the PI3K pathway at the cellular and molecular level, the development of PI3K inhibitors, and their clinical trials. Biomarkers, marine drugs, synthetic drugs, and repurposed drugs to treat breast cancer are also discussed, followed by mutational changes in PI3K and the resistance mechanism involved in PI3K inhibitors.