mTOR/AR signaling pathways blockade in castration-sensitive prostate cancer

Prostate Cancer (PCa) is the second most commonly diagnosed malignant disease and a major cause of death due to cancer among men worldwide. PCa is highly treatable in the early stages with surgery and Androgen Deprivation Therapy (ADT). However, most prostate cancer patients may develop resistance to ADT. This is often accompanied by the development of metastasis, which represents more than 90% of PCa related deaths.

   Mammalian target of rapamycin (mTOR) is a member of the phosphatidylinositol 3-kinase-related kinase family of protein kinases with a molecular weight of approximately 289 kDa. It has been found that the mTOR signaling pathway is overactivated in 40% of breast cancers and 50% of primary prostate cancers. Many mTOR inhibitors have been developed to treat human cancer. Rapalink-1, a bivalent compound that combines the durable effect of rapamycin and dual mTORC1/mTORC2 inhibition, has been shown the effectiveness in reducing PCa tumor growth in patient-derived xenografts (PDX) models. In this project, we aim to investigate the crosstalk relationship between AR and mTOR in castration-sensitive PCa.

Shuang Li