Biological Consequences of Radiation-induced DNA Damage: Relevance to Radiotherapy
TLDR
The concepts developed rely in part on the fact that ionising radiation creates significant levels of clustered DNA damage, including complex double-strand breaks (DSB), to kill tumour cells as clustered damage sites are difficult to repair.About:
This article is published in Clinical Oncology.The article was published on 2013-10-01 and is currently open access. It has received 509 citations till now. The article focuses on the topics: Radiation Induced DNA Damage & DNA damage.read more
Citations
More filters
Journal ArticleDOI
Mechanisms of DNA damage, repair, and mutagenesis.
TL;DR: This introductory review will delineate mechanisms of DNA damage and the counteracting repair/tolerance pathways to provide insights into the molecular basis of genotoxicity in cells that lays the foundation for subsequent articles in this issue.
Journal ArticleDOI
DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer.
Ruixue Huang,Ping-Kun Zhou +1 more
TL;DR: An update on the novel and promising druggable targets emerging from DDR pathways that can be exploited for radiosensitization is provided and challenges for ionizing radiation-induced signal transduction and targeted therapy are discussed.
Journal ArticleDOI
Opportunities and challenges of radiotherapy for treating cancer
Dörthe Schaue,William H. McBride +1 more
TL;DR: This Review focuses on how mechanistic processes might be targeted to improve the outcome of radiotherapy at the individual patient level, and would seem a more productive avenue of treatment than simply trying to increase the radiation dose delivered to the tumour.
Journal ArticleDOI
The MRE11–RAD50–NBS1 Complex Conducts the Orchestration of Damage Signaling and Outcomes to Stress in DNA Replication and Repair
TL;DR: MRN biochemistry provides prototypic insights into how it initiates, implements, and regulates multifunctional responses to genomic stress and its conformations change the paradigm whereby kinases initiate damage sensing.
Journal ArticleDOI
Pancreatic ductal adenocarcinoma: biological hallmarks, current status, and future perspectives of combined modality treatment approaches
M. Orth,M. Orth,Philipp Metzger,Philipp Metzger,Sabine Gerum,Julia Mayerle,Günter Schneider,Günter Schneider,Claus Belka,Maximilian Schnurr,Kirsten Lauber +10 more
TL;DR: New concepts combining distinct treatment modalities in order to improve therapeutic efficacy and clinical outcome are discussed – with a specific focus on protocols involving radio(chemo)therapeutic approaches.
References
More filters
Journal ArticleDOI
Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy
Hannah Farmer,Nuala McCabe,Christopher J. Lord,Andrew Tutt,Andrew Tutt,Damian A. Johnson,Tobias B. Richardson,Manuela Santarosa,Krystyna J. Dillon,Ian Hickson,Charlotte Knights,Niall M. B. Martin,Stephen P. Jackson,Graeme C. M. Smith,Alan Ashworth +14 more
TL;DR: BRCA1 or BRCA2 dysfunction unexpectedly and profoundly sensitizes cells to the inhibition of PARP enzymatic activity, resulting in chromosomal instability, cell cycle arrest and subsequent apoptosis, illustrating how different pathways cooperate to repair damage.
Journal ArticleDOI
Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase
Helen E. Bryant,Nilklas Schultz,Huw D. Thomas,Kayan M. Parker,Dan Flower,Elena Lopez,Suzanne Kyle,Mark Meuth,Nicola J. Curtin,Thomas Helleday,Thomas Helleday +10 more
TL;DR: It is proposed that, in the absence of PARP1, spontaneous single-strand breaks collapse replication forks and trigger homologous recombination for repair and exploited in order to kill BRCA2-deficient tumours by PARP inhibition alone.
Journal ArticleDOI
The Mechanism of Double-Strand DNA Break Repair by the Nonhomologous DNA End-Joining Pathway
TL;DR: Patients lacking normal NHEJ are not only sensitive to ionizing radiation (IR), but also severely immunodeficient in the range of DNA end substrate configurations upon which they can act.
Journal ArticleDOI
The Histological Structure of Some Human Lung Cancers and the Possible Implications for Radiotherapy
R H Thomlinson,L H Gray +1 more
TL;DR: The Histological Structure of Some Human Lung Cancers and the Possible Implications for Radiotherapy as mentioned in this paper, and the possible implications for radiotherapy for lung cancer diagnosis and treatment.
Journal ArticleDOI
Evidence for a lack of DNA double-strand break repair in human cells exposed to very low x-ray doses
Kai Rothkamm,Markus Löbrich +1 more
TL;DR: Evidence is presented that foci of γ-H2AX (a phosphorylated histone), detected by immunofluorescence, are quantitatively the same as DSBs and are capable of quantifying the repair of individual D SBs, allowing the investigation of DSB repair after radiation doses as low as 1 mGy, an improvement by several orders of magnitude over current methods.
Related Papers (5)
Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury
Evidence for a lack of DNA double-strand break repair in human cells exposed to very low x-ray doses
Kai Rothkamm,Markus Löbrich +1 more