Affiliation:
1. Division of Hematology and Oncology, Memorial Health Care, Pembroke Pines, FL 33028, USA
2. Division of Internal Medicine, Memorial Health Care, Pembroke Pines, FL 33028, USA
Abstract
The dysregulation of the phosphatidylinositol-3-kinase (PI3K) pathway can lead to uncontrolled cellular growth and tumorigenesis. Targeting PI3K and its downstream substrates has been shown to be effective in preclinical studies and phase III trials with the approval of several PI3K pathway inhibitors by the Food and Drug Administration (FDA) over the past decade. However, the limited clinical efficacy of these inhibitors, intolerable toxicities, and acquired resistances limit the clinical application of PI3K inhibitors. This review discusses the PI3K signaling pathway, alterations in the PI3K pathway causing carcinogenesis, current and novel PI3K pathway inhibitors, adverse effects, resistance mechanisms, challenging issues, and future directions of PI3K pathway inhibitors.
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis