Chapter 23 - Dramatic impact of partial loss of PTEN function on tumorigenesis and progression of prostate cancer

Abstract

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a phosphatase that metabolizes PIP3, the lipid product of PI 3-kinase, directly opposing the activation of the PI3K/AKT/mTOR oncogenic signaling network. Loss of the tumor suppressor PTEN, which negatively regulates the PI3K-AKT-mTOR pathway, is strongly linked to advanced prostate cancer progression and poor clinical outcomes. Thus, several therapeutic approaches are currently being explored to combat PTEN-deficient tumors. These include classical inhibition of the PI3K-AKT-mTOR signaling network, as well as novel approaches that restore PTEN function, or target PTEN regulation of chromosome stability, DNA damage repair, and the tumor microenvironment. However, targeting PTEN-deficient prostate cancer remains a clinical challenge. Therefore, we will refer to genetic mutations and loss of the protein as “PTEN loss” and discuss its impact on tumorigenesis and progression of prostate cancer.