(UroToday.com) In this session, Martin Gleave discusses alteration in the PI3K signaling pathway as an important molecular subtype of metastatic castration-resistant prostate cancer. Alterations in PI3K signaling contribute to the pathogenesis of many cancers. PTEN, a tumor suppressor that opposes the action of PI3K by converting PIP3 back to PIP2, is frequently lost in prostate cancer. PTEN loss is strongly linked to prostate carcinogenesis, disease progression, treatment resistance, and overall poor clinical outcomes. The mechanisms leading to loss of PTEN expression are cancer-specific, and different cancers harbor other various mechanisms of increased PI3K signaling, including PIK3CA mutations and AKT activating mutations. Upwards of 40% of mCRPC harbor genomic disruption of PTEN, most commonly homozygous deletion.