Chemo- and Radiosensitization Through Inhibition of PI3K/Akt Signaling.

Tumorigenesis and tumor progression are the consequences of disturbed balance between cell proliferation, differentiation, and programmed cell death. Additional processes including loss of cellular polarity, increased motility, and invasiveness lead to metastases resulting in spread of the tumor beyond the original site and account for the majority of morbidity and mortality from cancer. The phosphatidylinositol 3-kinase (PI3K) pathway, composed of multiple intracellular signaling proteins, controls various pivotal cellular functions related to cancer biology including cell proliferation, cell survival, migration, and vascularization. Major components of this pathway, including PI3K isoforms, phosphatase and tensin homolog (PTEN), phosphoinositide-dependent kinase 1 (PDK1), Akt, and mTOR, are frequently dysregulated by mutation, amplification, or rearrangement in multiple cancer lineages. These genetic aberrations render cancer cells sensitive to the inhibition of PI3K pathway at various levels. Targeting the PI3K/Akt pathway demonstrates marked efficacy in preclinical models. The PI3K signaling pathway has emerged as a high-quality therapeutic target in cancer treatment. [ABSTRACT FROM AUTHOR]