Prostate Cancer and PTEN/PI3K/AKT/mTOR Signaling

Despite the generally positive prognosis seen in patients with localized prostate cancer after surgical intervention and their excellent response to androgen-deprivation treatment, it’s crucial to emphasize that about one-third of these individuals inevitably experience recurrence and subsequently develop castration-resistant prostate cancer (CRPC). Generally, the effectiveness of prostate cancer treatment is limited, highlighting the need to develop alternative treatments that might improve the outcomes of hormone administration and/or surgical castration. The abnormal regulation of the phosphoinositide 3-kinase (PI3K) pathway has become a subject of increasing interest in the context of prostate cancer. This is primarily because of the regular occurrences of post-translational modifications, epigenetic alterations, and genetic mutations affecting both PI3K and phosphatase and tensin homolog (PTEN). These alterations have been entangled in the development and advancement of prostate cancer and in the resistance to conventional androgen-deprivation treatment. In this chapter, we provide a comprehensive overview of the cellular activities of the key components involved in this cascade, as well as their dysregulation in prostate cancer. We also summarize the findings from both preclinical and clinical investigations, including inhibitors of PI3K signaling, and examine the non-genomic factors contributing to the lack of success in these therapeutic interventions.