Deficiency in Homologous Recombination Renders Mammalian Cells More Sensitive to Proton Versus Photon Irradiation

Grosse, Nicole; Fontana, A.; Hug, Eugen B.; Lomax, Antony; Coray, A.; Augsburger, Marc A.; Paganetti, Harald; Sartori, Alessandro A.; Pruschy, Martin

doi:10.1016/j.ijrobp.2013.09.041

Cited by 109 publications

(126 citation statements)

References 34 publications

Supporting

Mentioning

117

Contrasting

Order By: Relevance

“…Several experimental works support the hypothesis that the kinetics of double strand break repair is governed by complexity of DSB [5,23,39,[49][50][51][52]. In a recent publication, our hypothesis was experimentally confirmed [53]. Their results clearly showed that HR mutated cells were more sensitive to proton than to photon exposure.…”

Section: Discussionsupporting

confidence: 76%

DSB repair model for mammalian cells in early S and G1 phases of the cell cycle: Application to damage induced by ionizing radiation of different quality

Taleei

Girard

Nikjoo

2015

Mutation Research/Genetic Toxicology and Environmental Mutagene

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 76%

DSB repair model for mammalian cells in early S and G1 phases of the cell cycle: Application to damage induced by ionizing radiation of different quality

Taleei

Girard

Nikjoo

2015

Mutation Research/Genetic Toxicology and Environmental Mutagene

View full text Add to dashboard Cite

“…Although hyperthermia itself is advancing beyond previous possibilities, the collection of possible synergising agents are also emerging. With the expanding interest in the use of proton therapy in oncology, it has been suggested that cells harbouring defects in homologous recombination are more sensitive towards proton irradiation than to photon irradiation [112,113]. Since, as we explained above, heat causes a defect in homologous recombination, there is a rational basis for the combination of hyperthermia with proton therapy.…”

Section: The Future Of Hyperthermiamentioning

confidence: 99%

Improving efficacy of hyperthermia in oncology by exploiting biological mechanisms

Tempel¹,

Horsman

Kanaar³

2016

International Journal of Hyperthermia

102

View full text Add to dashboard Cite

It has long been established that hyperthermia increases the therapeutic benefit of radiation and chemotherapy in cancer treatment. During the last few years there have been substantial technical improvements in the sources used to apply and measure heat, which greatly increases enthusiasm for the clinical use of hyperthermia. These advances are converging with a better understanding of the physiological and molecular effects of hyperthermia. Therefore, we are now at a juncture where the parameters that will influence the efficacy of hyperthermia in cancer treatment can be optimised in a more systematic and rational manner. In addition, the novel insights in hyperthermia's many biological effects on tumour cells will ultimately result in new treatment regimes. For example, the molecular effects of hyperthermia on the essential cellular process of DNA repair suggest novel combination therapies, with DNA damage response targeting drugs that should now be clinically explored. Here, we provide an overview of recent studies on the various macroscopic and microscopic biological effects of hyperthermia. We indicate the significance of these effects on current treatments and suggest how they will help design novel future treatments. ARTICLE HISTORY

show abstract

“…It has even been suggested that protons induce more DNA damage than heavier ions at the same LET [24]. In addition, evidence indicates that altered patterns of repair occur, including a preference for homologous recombination in cells irradiated with protons and greater sensitivity when it is defective [25, 26]. Other differences in biological effects include production of reactive oxygen species [27], complex chromosomal alterations [28], micronuclei, and apoptosis [29].…”

Section: Importance Of Radiogenomic Research For Patients Treated Witmentioning

confidence: 99%

Radiogenomic Predictors of Adverse Effects following Charged Particle Therapy

Morton

Ricks-Santi

West

et al. 2018

International Journal of Particle Therapy

View full text Add to dashboard Cite

Radiogenomics is the study of genomic factors that are associated with response to radiation therapy. In recent years, progress has been made toward identifying genetic risk factors linked with late radiation-induced adverse effects. These advances have been underpinned by the establishment of an international Radiogenomics Consortium with collaborative studies that expand cohort sizes to increase statistical power and efforts to improve methodologic approaches for radiogenomic research. Published studies have predominantly reported the results of research involving patients treated with photons using external beam radiation therapy. These studies demonstrate our ability to pool international cohorts to identify common single nucleotide polymorphisms associated with risk for developing normal tissue toxicities. Progress has also been achieved toward the discovery of genetic variants associated with radiation therapy–related subsequent malignancies. With the increasing use of charged particle therapy (CPT), there is a need to establish cohorts for patients treated with these advanced technology forms of radiation therapy and to create biorepositories with linked clinical data. While some genetic variants are likely to impact toxicity and second malignancy risks for both photons and charged particles, it is plausible that others may be specific to the radiation modality due to differences in their biological effects, including the complexity of DNA damage produced. In recognition that the formation of patient cohorts treated with CPT for radiogenomic studies is a high priority, efforts are underway to establish collaborations involving institutions treating cancer patients with protons and/or carbon ions as well as consortia, including the Proton Collaborative Group, the Particle Therapy Cooperative Group, and the Pediatric Proton Consortium Registry. These important radiogenomic CPT initiatives need to be expanded internationally to build on experience gained from the Radiogenomics Consortium and epidemiologists investigating normal tissue toxicities and second cancer risk.

show abstract

Deficiency in Homologous Recombination Renders Mammalian Cells More Sensitive to Proton Versus Photon Irradiation

Cited by 109 publications

References 34 publications

DSB repair model for mammalian cells in early S and G1 phases of the cell cycle: Application to damage induced by ionizing radiation of different quality

DSB repair model for mammalian cells in early S and G1 phases of the cell cycle: Application to damage induced by ionizing radiation of different quality

Improving efficacy of hyperthermia in oncology by exploiting biological mechanisms

Radiogenomic Predictors of Adverse Effects following Charged Particle Therapy

Contact Info

Product

Resources

About