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Castration radiosen...
Castration radiosensitizes prostate cancer tissue by impairing DNA double-strand break repair
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- Tarish, Firas L. (författare)
- Karolinska Institutet
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- Schultz, Niklas (författare)
- Karolinska Institutet
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- Tanoglidi, Anna (författare)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Hamberg, Hans (författare)
- Cent Hosp Vasteras, Dept Pathol, S-72189 Vasteras, Sweden.
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- Letocha, Henry (författare)
- Cent Hosp Vasteras, Dept Oncol, S-72189 Vasteras, Sweden.
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- Karaszi, Katalin (författare)
- Univ Oxford, Dept Oncol, Oxford Inst Radiat Oncol, Oxford OX3 9DU, England.
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- Hamdy, Freddie C. (författare)
- Univ Oxford, Dept Oncol, Oxford Inst Radiat Oncol, Oxford OX3 9DU, England.
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- Granfors, Torvald (författare)
- Cent Hosp Vasteras, Dept Urol, S-72189 Vasteras, Sweden.
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- Helleday, Thomas (författare)
- Karolinska Institutet
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(creator_code:org_t)
- American Association for the Advancement of Science (AAAS), 2015
- 2015
- Engelska.
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 7:312
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
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- 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 non-homologous 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 gamma-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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
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