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Selective DNA-PKcs inhibition extends the therapeutic index of localized radiotherapy and chemotherapy

Abstract:

Potentiating radiotherapy and chemotherapy by inhibiting DNA damage repair is proposed as a therapeutic strategy to improve outcomes for patients with solid tumors. However, this approach risks enhancing normal tissue toxicity as much as tumor toxicity, thereby limiting its translational impact. Using NU5455, a newly identified highly selective oral inhibitor of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) activity, we found that it was indeed possible to preferentially augment t...

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Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1172/JCI127483

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Role:
Author
ORCID:
0000-0002-0617-8833
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Role:
Author
ORCID:
0000-0001-6014-811X
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Publisher:
American Society for Clinical Investigation Publisher's website
Journal:
Journal of clinical investigation Journal website
Volume:
130
Issue:
1
Pages:
258-271
Publication date:
2020-01-01
Acceptance date:
2019-09-25
DOI:
EISSN:
1558-8238
ISSN:
0021-9738
Pmid:
31581151
Language:
English
Keywords:
Pubs id:
1074835
Local pid:
pubs:1074835
Deposit date:
2020-03-10

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