바로가기  >

Abstract
Clinical trials have established the benefit of androgen deprivation therapy (ADT) combined with radiotherapy in prostate cancer. ADT sensitizes prostate cancer to radiotherapy-induced death at least in part through inhibition of DNA repair machinery, but for unknown reasons, adjuvant ADT provides further survival benefits. Here, we show that androgen receptor (AR) expression and activity are durably upregulated following radiotherapy in multiple human prostate cancer models in vitro and in vivo. Moreover, the degree of AR upregulation correlates with survival in vitro and time to tumor progression in animal models. We also provide evidence of AR pathway upregulation, measured by a rise in serum levels of AR-regulated hK2 protein, in nearly 20% of patients after radiotherapy. Furthermore, these men were three-fold more likely to experience subsequent biochemical failure. Collectively, these data demonstrate that radiotherapy can upregulate AR signaling after therapy to an extent that negatively affects disease progression and/or survival.​

Spratt DE1, Evans MJ2, Davis BJ3, Doran MG4, Lee MX2, Shah N2, Wongvipat J2, Carnazza KE4, Klee GG5, Polkinghorn W6, Tindall DJ5, Lewis JS7, Sawyers CL8.

1Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. Human Oncology Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York. Department of Radiology and Molecular the Molecular Pharmacology & Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York.
2Human Oncology Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
3Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota.
4Department of Radiology and Molecular the Molecular Pharmacology & Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York.
5Departments of Urology and Biochemistry/Molecular Biology, Mayo Clinic, Rochester, Minnesota.
6Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. Human Oncology Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
7Department of Radiology and Molecular the Molecular Pharmacology & Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York. sawyersc@mskcc.org lewisj2@mskcc.org.
8Human Oncology Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York. sawyersc@mskcc.org lewisj2@mskcc.org.