DNA Repair Alterations in Children With Pediatric Malignancies: Novel Opportunities to Identify Patients at Risk for High-Grade Toxicities

Rübe, Claudia E.; Fricke, Andreas; Schneider, Ruth; Simon, Karin; Kühne, Martin; Fleckenstein, Jochen; Gräber, Stefan; Graf, Norbert; Rübe, Christian

doi:10.1016/j.ijrobp.2009.08.052

Cited by 63 publications

(43 citation statements)

References 55 publications

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“…These data indicate that the gH2AX foci assay could be able to identify a repair defect in some individual extremely overreacting patients. It, however, cannot be used to identify patients who are at risk to suffer from serious side effects following a (chemo)radiotherapy course (Rü be et al 2010). …”

Section: Discussionmentioning

confidence: 99%

Lack of a correlation between γH2AX foci kinetics in lymphocytes and the severity of acute normal tissue reactions during IMRT treatment for head and neck cancer

Werbrouck

Duprez

Neve

et al. 2010

International Journal of Radiation Biology

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Section: Discussionmentioning

confidence: 99%

Lack of a correlation between γH2AX foci kinetics in lymphocytes and the severity of acute normal tissue reactions during IMRT treatment for head and neck cancer

Werbrouck

Duprez

Neve

et al. 2010

International Journal of Radiation Biology

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“…Persistence of gH2AX was significantly higher in lymphocytes from children with pediatric cancer compared with age-matched control children 8 h after exposure of whole blood with 1 Gy and 2 Gy of X-rays. While all healthy children exhibited efficient DNA repair, three children with pediatric cancer had impaired DNA repair capacity and two out of these three children developed acute normal tissue toxicity, which may be indicative of impaired DNA repair [87]. The measure of persistence of gH2AX can be a predictive assay in identifying those individuals at the greatest risk for the development of adverse effects to radiotherapy or chemotherapy.…”

Section: Peripheral Blood Mononuclear Cellsmentioning

confidence: 99%

Persistent γH2AX: A promising molecular marker of DNA damage and aging

Siddiqui

François

Fenech

et al. 2015

Mutation Research/Reviews in Mutation Research

182

142

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“…The foci assay could best detect a correlation of γ-H2AX signal and acute oral mucositis and dermatitis (grade ≥3) 123 . In two studies with 41 and 47 pediatric solid tumors and leukemia patients receiving DNA-damaging therapy, γ-H2AX foci were evaluated in ex-vivo irradiated PBL which enabled the identification of patients at risk for high-grade acute and late toxicities and allowed for detection of DSB repair deficiencies, although not all treatment-associated normal-tissue toxicities could be explained by DSB repair insufficiencies 124 , 125 . Similar observations were made with regard to severe late effects in prostate cancer patients and acute (grade >2) dermatitis in breast cancer patients 106 , 126 .…”

Section: γ-H2ax Assays For Biodosimetry and Prediction Of Normal Tissmentioning

confidence: 99%

DNA Damage Response Assessments in Human Tumor Samples Provide Functional Biomarkers of Radiosensitivity

Willers

Gheorghiu

Liu

et al. 2015

Seminars in Radiation Oncology

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Predictive biomarkers are urgently needed for individualization of radiation therapy and treatment with radiosensitizing anti-cancer agents. Genomic profiling of human cancers will provide us with unprecedented insight into the mutational landscape of genes directly or indirectly involved in the response to radiation-induced DNA damage. However, to what extent this wealth of structural information about the cancer genome will produce biomarkers of sensitivity to radiation remains to be seen. Investigators are increasingly studying the subnuclear accumulation (i.e., foci) of proteins in the DNA damage response (DDR), such as γ-H2AX, 53BP1, or RAD51, as a surrogate of treatment sensitivity. Recent findings from preclinical studies have demonstrated the predictive potential of DDR foci by correlating foci with clinically relevant endpoints such as tumor control probability. Therefore, pre-clinical investigations of DDR foci responses are increasingly moving into cells and tissues from patients, which is the major focus of this review. The advantage of using DDR foci as functional biomarkers is that they can detect alterations in DNA repair due to various mechanisms. Moreover, they provide a global measurement of DDR network function without needing to know the identities of all the components, many of which remain unknown. Foci assays are thus expected to yield functional insight that may complement or supersede genomic information, thereby giving radiation oncologists unique opportunities to individualize cancer treatments in the near future.

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DNA Repair Alterations in Children With Pediatric Malignancies: Novel Opportunities to Identify Patients at Risk for High-Grade Toxicities

Cited by 63 publications

References 55 publications

Lack of a correlation between γH2AX foci kinetics in lymphocytes and the severity of acute normal tissue reactions during IMRT treatment for head and neck cancer

Lack of a correlation between γH2AX foci kinetics in lymphocytes and the severity of acute normal tissue reactions during IMRT treatment for head and neck cancer

Persistent γH2AX: A promising molecular marker of DNA damage and aging

DNA Damage Response Assessments in Human Tumor Samples Provide Functional Biomarkers of Radiosensitivity

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