New molecular targets in radiotherapy
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New molecular targets in radiotherapy : DNA damage signalling and repair in targeted and non-targeted cells. / Burdak-Rothkamm, Susanne; Prise, Kevin M.
In: EUR J PHARMACOL, Vol. 625, No. 1-3, 25.12.2009, p. 151-5.Research output: SCORING: Contribution to journal › SCORING: Review article › Research
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TY - JOUR
T1 - New molecular targets in radiotherapy
T2 - DNA damage signalling and repair in targeted and non-targeted cells
AU - Burdak-Rothkamm, Susanne
AU - Prise, Kevin M
PY - 2009/12/25
Y1 - 2009/12/25
N2 - Ionising radiation plays a key role in therapy due to its ability to directly induce DNA damage, in particular DNA double-strand breaks leading to cell death. Cells have multiple repair pathways which attempt to maintain genomic stability. DNA repair proteins have become key targets for therapy, using small molecule inhibitors, in combination with radiation and or chemotherapeutic agents as a means of enhancing cell killing. Significant advances in our understanding of the response of cells to radiation exposures has come from the observation of non-targeted effects where cells respond via mechanisms other than those which are a direct consequence of energy-dependent DNA damage. Typical of these is bystander signalling where cells respond to the fact that their neighbours have been irradiated. Bystander cells show a DNA damage response which is distinct from directly irradiated cells. In bystander cells, ATM- and Rad3-related (ATR) protein kinase-dependent signalling in response to stalled replication forks is an early event in the DNA damage response. The ATM protein kinase is activated downstream of ATR in bystander cells. This offers the potential for differential approaches for the modulation of bystander and direct effects with repair inhibitors which may impact on the response of tumours and on the protection of normal tissues during radiotherapy.
AB - Ionising radiation plays a key role in therapy due to its ability to directly induce DNA damage, in particular DNA double-strand breaks leading to cell death. Cells have multiple repair pathways which attempt to maintain genomic stability. DNA repair proteins have become key targets for therapy, using small molecule inhibitors, in combination with radiation and or chemotherapeutic agents as a means of enhancing cell killing. Significant advances in our understanding of the response of cells to radiation exposures has come from the observation of non-targeted effects where cells respond via mechanisms other than those which are a direct consequence of energy-dependent DNA damage. Typical of these is bystander signalling where cells respond to the fact that their neighbours have been irradiated. Bystander cells show a DNA damage response which is distinct from directly irradiated cells. In bystander cells, ATM- and Rad3-related (ATR) protein kinase-dependent signalling in response to stalled replication forks is an early event in the DNA damage response. The ATM protein kinase is activated downstream of ATR in bystander cells. This offers the potential for differential approaches for the modulation of bystander and direct effects with repair inhibitors which may impact on the response of tumours and on the protection of normal tissues during radiotherapy.
KW - Antineoplastic Agents/pharmacology
KW - Bystander Effect/radiation effects
KW - Cell Cycle/radiation effects
KW - Combined Modality Therapy
KW - DNA Breaks, Double-Stranded/radiation effects
KW - DNA Damage/radiation effects
KW - DNA Repair/drug effects
KW - Humans
KW - Neoplasms/drug therapy
KW - Radiation, Ionizing
KW - Signal Transduction/radiation effects
U2 - 10.1016/j.ejphar.2009.09.068
DO - 10.1016/j.ejphar.2009.09.068
M3 - SCORING: Review article
C2 - 19835868
VL - 625
SP - 151
EP - 155
JO - EUR J PHARMACOL
JF - EUR J PHARMACOL
SN - 0014-2999
IS - 1-3
ER -
