The pentose phosphate pathway - targeting metabolism to prevent advanced prostate cancer

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Once prostate cancer spreads to bone (bone metastases) there is no cure. To develop new ways to combat this fatal stage, we need to understand exactly how it grows and spreads. Prostate cancer cells need energy to grow. We think specific changes in the energy needs of prostate cancer help prostate cancer grow within bone, and that bone cells talk to prostate cancer cells to cause these changes. We have discovered a specific energy pathway, the pentose phosphate pathway (PPP) that is increased in bone metastatic prostate cancer. When we block this pathway, tumour growth is reduced. We will investigate exactly how the PPP causes prostate cancer bone metastases and whether blocking the PPP, either alone or in combination with current clinical approaches, is effective in reducing tumour burden and bone disease. We will grow human prostate cancer cells in contact with bone cells, mimicking the situation in the human body, and we will increase/decrease the PPP and see how this changes prostate cancer cell growth, death and movement (representing metastatic spread). We will use in vivo (mouse) models to investigate blocking the PPP in prostate cancer bone metastases. This project will uncover the function and potential of the PPP as a novel treatment for bone metastatic prostate cancer.