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

磷酸戊糖途径 - 靶向代谢以预防晚期前列腺癌

• 批准号: MR/X000834/1
• 负责人: Claire Edwards
• 金额: $ 83.53万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FX000834%2F1
• 关键词: pentose; phosphate; pathway; targeting; metabolism

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.

一旦前列腺癌扩散到骨骼（骨转移），就无法治愈。为了开发对抗这一致命阶段的新方法，我们需要确切地了解它是如何生长和传播的。前列腺癌细胞生长需要能量。我们认为前列腺癌能量需求的特定变化有助于前列腺癌在骨内生长，而骨细胞与前列腺癌细胞对话导致这些变化。我们已经发现了一种特殊的能量途径，戊糖磷酸途径（PPP）在骨转移性前列腺癌中增加。当我们阻断这一途径时，肿瘤的生长就会减少。我们将研究PPP是如何导致前列腺癌骨转移的，以及阻断PPP是否能有效减少肿瘤负担和骨病，无论是单独还是与目前的临床方法相结合。我们将在与骨细胞接触的情况下培养人类前列腺癌细胞，模拟人体的情况，我们将增加/减少PPP，看看这如何改变前列腺癌细胞的生长、死亡和运动（代表转移性扩散）。我们将使用体内（小鼠）模型来研究阻断PPP在前列腺癌骨转移中的作用。该项目将揭示PPP作为骨转移性前列腺癌新疗法的功能和潜力。