Targeting PI3K/Akt signaling in prostate cancer therapy

Abstract

Urological cancers have obtained much attention in recent years due to their mortality and morbidity. The most common and malignant tumor of urological cancers is prostate cancer that imposes high socioeconomic costs on public life and androgen-deprivation therapy, surgery, and combination of chemotherapy and radiotherapy are employed in its treatment. PI3K/Akt signaling is an oncogenic pathway responsible for migration, proliferation and drug resistance in various cancers. In the present review, the role of PI3K/Akt signaling in prostate cancer progression is highlighted. The activation of PI3K/Akt signaling occurs in prostate cancer, while PTEN as inhibitor of PI3K/Akt shows down-regulation. Stimulation of PI3K/Akt signaling promotes survival of prostate tumor cells and prevents apoptosis. The cell cycle progression and proliferation rate of prostate tumor cells increase by PI3K/Akt signaling induction. PI3K/Akt signaling stimulates EMT and enhances metastasis of prostate tumor cells. Silencing PI3K/Akt signaling impairs growth and metastasis of prostate tumor cells. Activation of PI3K/Akt signaling mediates drug resistance and reduces radio-sensitivity of prostate tumor cells. Anti-tumor compounds suppress PI3K/Akt signaling in impairing prostate tumor progression. Furthermore, upstream regulators such as miRNAs, lncRNAs and circRNAs regulate PI3K/Akt signaling and it has clinical implications for prostate cancer patients.

Keywords: Anti-cancer agents; Cancer therapy; Chemoresistance; PI3K/Akt; Prostate cancer.