The PI3K pathway is a major source of drug resistance in prostate cancer. This is particularly true in castration-resistant prostate cancer, where tumours become resistant to androgen-deprivation therapy, which block the tumours ability to utilise the hormone androgen to grow. This is due to a complex feedback mechanism which exists between the androgen receptor and the PI3K pathway. As in other tumour types, mutations in key genes of this pathway can lead to hyperactivation of this pathway, for example in PIK3CA, Increases in the copy number of PIK3CA and increased mRNA expression also increases pathway activation in prostate cancers among others. Gains in the nearby genetic region 3q26.31-32 have been shown to co-occur with a number of nearby PI3K family members including PIK3CA, PIK3CB and PIK3R4, leading to transcriptional changes in PIK3C2G, PIK3CA, PIK3CB, PIK3R4 as well as pathways associated with cell proliferation. These large spanning gains associate with Gleason grade, tumour stage, lymph node metastasis and other aggressive clinical features. In patients treated with PI3K inhibitors, those with copy number gains in PIK3CB appear to have increased drug susceptibility.