Castration radiosensitizes prostate cancer tissue by impairing DNA double-strand break repair
| Autor: | Katalin Karaszi, Niklas Schultz, Torvald Granfors, Firas Tarish, Anna Tanoglidi, Hans Hamberg, Henry Letocha, Thomas Helleday, Freddie C. Hamdy |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Adult
Male Oncology Radiation-Sensitizing Agents medicine.medical_specialty DNA repair medicine.medical_treatment Biology Radiation Tolerance Histones Young Adult chemistry.chemical_compound Prostate cancer Internal medicine medicine Humans DNA Breaks Double-Stranded Orchiectomy Chemical castration Aged Aged 80 and over Ku70 fungi Prostatic Neoplasms Cancer General Medicine Middle Aged medicine.disease DNA-Binding Proteins Gene Expression Regulation Neoplastic Radiation therapy enzymes and coenzymes (carbohydrates) DNA Repair Enzymes Castration chemistry Receptors Androgen |
| Zdroj: | Science Translational Medicine. 7 |
| ISSN: | 1946-6242 1946-6234 |
| DOI: | 10.1126/scitranslmed.aac5671 |
| Popis: | Chemical castration improves responses to radiotherapy in prostate cancer, but the mechanism is unknown. We hypothesized that this radiosensitization is caused by castration-mediated down-regulation of nonhomologous end joining (NHEJ) repair of DNA double-strand breaks (DSBs). To test this, we enrolled 48 patients with localized prostate cancer in two arms of the study: either radiotherapy first or radiotherapy after neoadjuvant castration treatment. We biopsied patients at diagnosis and before and after castration and radiotherapy treatments to monitor androgen receptor, NHEJ, and DSB repair in verified cancer tissue. We show that patients receiving neoadjuvant castration treatment before radiotherapy had reduced amounts of the NHEJ protein Ku70, impaired radiotherapy-induced NHEJ activity, and higher amounts of unrepaired DSBs, measured by γ-H2AX foci in cancer tissues. This study demonstrates that chemical castration impairs NHEJ activity in prostate cancer tissue, explaining the improved response of patients with prostate cancer to radiotherapy after chemical castration. |
| Databáze: | OpenAIRE |
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