DNA Repair.
Cellular chromosomal DNA is the principal target through which ionising radiation exerts it diverse biological effects. This chapter summarises the relevant DNA damage signalling and repair pathways used by normal and tumour cells in response to irradiation. Strategies for tumour radiosensitisation are reviewed which exploit tumour-specific DNA repair deficiencies or signalling pathway addictions, with a special focus on growth factor signalling, PARP, cancer stem cells, cell cycle checkpoints and DNA replication. This chapter concludes with a discussion of DNA repair-related candidate biomarkers of tumour response which are of crucial importance for implementing precision medicine in radiation oncology.
Laboratory of Radiobiology and Experimental Radio-Oncology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
Kerstin
K
Borgmann
Laboratory of Radiobiology and Experimental Radio-Oncology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
Sabrina
S
Köcher
Laboratory of Radiobiology and Experimental Radio-Oncology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
Malte
M
Kriegs
Laboratory of Radiobiology and Experimental Radio-Oncology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
Wael Yassin
WY
Mansour
Laboratory of Radiobiology and Experimental Radio-Oncology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
Ann Christin
AC
Parplys
Laboratory of Radiobiology and Experimental Radio-Oncology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.|Department of Otorhinolaryngology and Head and Neck Surgery, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
Thorsten
T
Rieckmann
Laboratory of Radiobiology and Experimental Radio-Oncology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. k.rothkamm@uke.de.
Kai
K
Rothkamm
D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects*; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication / Q000235:genetics / Q000528:radiation effects; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D053263:Gene Regulatory Networks / Q000528:radiation effects; D006801:Humans; D008957:Models, Genetic; D009369:Neoplasms / Q000235:genetics / Q000532:radiotherapy*; D015398:Signal Transduction / Q000235:genetics / Q000528:radiation effects
Biomarkers; DNA damage response; DNA double-strand break repair; DNA strand breaks; Ionising radiation; Molecular targeting