Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - DNA end-processing enzyme polynucleotide kinase as a potential target in the treatment of cancer
AU - Allinson, Sarah
PY - 2010
Y1 - 2010
N2 - Pharmacological inhibition of DNA-repair pathways as an approach for the potentiation of chemo- and radio-therapeutic cancer treatments has attracted increasing levels of interest in recent years. Inhibitors of several enzymes involved in the repair of DNA strand breaks are currently at various stages of the drug development process. Polynucleotide kinase (PNK), a bifunctional DNA-repair enzyme that possesses both 3'-phosphatase and 5'-kinase activities, plays an important role in the repair of both single strand and double strand breaks and as a result, RNAi-mediated knockdown of PNK sensitizes cells to a range of DNA-damaging agents. Recently, a small molecule inhibitor of PNK has been developed that is able to sensitize cells to ionizing radiation and the topoisomerase I poison, camptothecin. Although still in the early stages of development, PNK inhibition represents a promising means of enhancing the efficacy of existing cancer treatments.
AB - Pharmacological inhibition of DNA-repair pathways as an approach for the potentiation of chemo- and radio-therapeutic cancer treatments has attracted increasing levels of interest in recent years. Inhibitors of several enzymes involved in the repair of DNA strand breaks are currently at various stages of the drug development process. Polynucleotide kinase (PNK), a bifunctional DNA-repair enzyme that possesses both 3'-phosphatase and 5'-kinase activities, plays an important role in the repair of both single strand and double strand breaks and as a result, RNAi-mediated knockdown of PNK sensitizes cells to a range of DNA-damaging agents. Recently, a small molecule inhibitor of PNK has been developed that is able to sensitize cells to ionizing radiation and the topoisomerase I poison, camptothecin. Although still in the early stages of development, PNK inhibition represents a promising means of enhancing the efficacy of existing cancer treatments.
U2 - 10.2217/fon.10.40
DO - 10.2217/fon.10.40
M3 - Journal article
VL - 6
SP - 1031
EP - 1042
JO - Future Oncology
JF - Future Oncology
SN - 1479-6694
IS - 6
ER -