Radiation Biomarkers: Silver Bullet, or Wild Goose Chase?

Rutten, Eric Andreas; Badie, Christophe

doi:10.3390/jpm11070603

Cited by 6 publications

(3 citation statements)

References 19 publications

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“…Studies of molecular and genetic markers and genome-wide association studies (GWAS) offer the promise of better understanding the mechanistic processes involved in therapy-related cancer (Morton et al 2017b); Rutten and Badie (2021) have provided a précis of the current status of radiation biomarkers. It is established that chromosome translocation frequencies in peripheral blood lymphocytes are a reflection of dose to the ABM if measured in stable cells (Tawn and Whitehouse 2003), and micronuclei frequencies in solid cancer cells following radiotherapy have recently been reported by Kobayashi et al (2020).…”

Section: Risk Of Second Primary Cancers After Radiotherapymentioning

confidence: 99%

The risk of cancer following high, and very high, doses of ionising radiation

Wakeford

Hauptmann

2022

J. Radiol. Prot.

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It is established that moderate-to-high doses of ionising radiation increase the risk of subsequent cancer in the exposed individual, but the question arises as to the risk of cancer from higher doses, such as those delivered during radiotherapy, accidents, or deliberate acts of malice. In general, the cumulative dose received during a course of radiation treatment is sufficiently high that it would kill a person if delivered as a single dose to the whole body, but therapeutic doses are carefully fractionated and high/very high doses are generally limited to a small tissue volume under controlled conditions. The very high cumulative doses delivered as fractions during radiation treatment are designed to inactivate diseased cells, but inevitably some healthy cells will also receive high/very high doses. How the doses (ranging from <1 Gy to tens of Gy) received by healthy tissues during radiotherapy affect the risk of second primary cancer is an increasingly important issue to address as more cancer patients survive the disease. Studies show that, except for a turndown for thyroid cancer, a linear dose-response for second primary solid cancers seems to exist over a cumulative gamma radiation dose range of tens of gray, but with a gradient of excess relative risk (ERR) per Gy that varies with the type of second cancer, and which is notably shallower than that found in the Japanese atomic bomb survivors receiving a single moderate-to-high acute dose. The risk of second primary cancer consequent to high/very high doses of radiation is likely to be due to repopulation of heavily irradiated tissues by surviving stem cells, some of which will have been malignantly transformed by radiation exposure, although the exact mechanism is not known, and various models have been proposed. It is important to understand the mechanisms that lead to the raised risk of second primary cancers consequent to the receipt of high/very high doses, in particular so that the risks associated with novel radiation treatment regimens – for example, intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) that deliver high doses to the target volume while exposing relatively large volumes of healthy tissue to low/moderate doses, and treatments using protons or heavy ions rather than photons – may be properly assessed.

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Section: Risk Of Second Primary Cancers After Radiotherapymentioning

confidence: 99%

The risk of cancer following high, and very high, doses of ionising radiation

Wakeford

Hauptmann

2022

J. Radiol. Prot.

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“…Biomarkers have been at the forefront of discussion and research within radiation biology for several years, as they can potentially exhibit biological processes closely related to the mechanism of disease 4,10,11 . In radiation exposed individuals, biomarkers that can assess absorbed radiation doses as well as predict health decline are needed so that treatments can be applied that will ultimately improve overall patient outcome [12][13][14] .…”

Section: Introductionmentioning

confidence: 99%

Proteomic Analysis of Plasma at the Preterminal Stage of Rhesus Nonhuman Primates Exposed to a Lethal Total-Body Dose of Gamma-Radiation

Carpenter,

Fatanmi,

Wise

et al. 2024

Preprint

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The identification and validation of radiation biomarkers is critical for assessing the radiation dose received in exposed individuals and for developing radiation medical countermeasures that can be used to treat acute radiation syndrome (ARS). Additionally, a fundamental understanding of the effects of radiation injury could further aid in the identification and development of therapeutic targets for mitigating radiation damage. In this study, blood samples were collected from fourteen male nonhuman primates (NHPs) that were exposed to 7.2 Gy ionizing radiation at various time points (seven days prior to irradiation; 1, 13, and 25 days post-irradiation; as well as immediately prior to the euthanasia of moribund animals (preterminal)). Plasma was isolated from these samples and was analyzed using a liquid chromatography tandem mass spectrometry approach in an effort to determine the effects of radiation on plasma proteomic profiles. Of particular interest was to determine if the expression of certain proteins reacted to radiation in a way that would act as a predictor for health decline leading to a preterminal phenotype. Our results suggest that radiation induced a diverse temporal pattern among protein expression that displayed prominent changes within NHP proteomic plasma profiles. Of these significantly altered proteins, several play important roles in certain biological processes such as hemostasis, inflammation, and immune response.

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“…Biomarkers have been at the forefront of discussion and research within the radiation biology community for several years, as they can potentially exhibit biological processes closely related to the mechanism of disease 4 , 10 , 11 . In radiation exposed individuals, biomarkers that can be used to assess absorbed radiation doses as well as predict health decline are needed so that treatments can be applied to ultimately improve overall patient outcome 12 – 14 .…”

Section: Introductionmentioning

confidence: 99%

Proteomic analysis of plasma at the preterminal stage of rhesus nonhuman primates exposed to a lethal total-body dose of gamma-radiation

Carpenter,

Fatanmi,

Wise

et al. 2024

Sci Rep

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The identification and validation of radiation biomarkers is critical for assessing the radiation dose received in exposed individuals and for developing radiation medical countermeasures that can be used to treat acute radiation syndrome (ARS). Additionally, a fundamental understanding of the effects of radiation injury could further aid in the identification and development of therapeutic targets for mitigating radiation damage. In this study, blood samples were collected from fourteen male nonhuman primates (NHPs) that were exposed to 7.2 Gy ionizing radiation at various time points (seven days prior to irradiation; 1, 13, and 25 days post-irradiation; and immediately prior to the euthanasia of moribund (preterminal) animals). Plasma was isolated from these samples and was analyzed using a liquid chromatography tandem mass spectrometry approach in an effort to determine the effects of radiation on plasma proteomic profiles. The primary objective was to determine if the radiation-induced expression of specific proteins could serve as an early predictor for health decline leading to a preterminal phenotype. Our results suggest that radiation induced a complex temporal response in which some features exhibit upregulation while others trend downward. These statistically significantly altered features varied from pre-irradiation levels by as much as tenfold. Specifically, we found the expression of integrin alpha and thrombospondin correlated in peripheral blood with the preterminal stage. The differential expression of these proteins implicates dysregulation of biological processes such as hemostasis, inflammation, and immune response that could be leveraged for mitigating radiation-induced adverse effects.

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Radiation Biomarkers: Silver Bullet, or Wild Goose Chase?

Abstract: Humans have learned to harness the power of radiation for therapeutic ends, with 50% of all patients diagnosed with cancer undergoing radiotherapy as part of their treatment [...]

Cited by 6 publications

References 19 publications

The risk of cancer following high, and very high, doses of ionising radiation

The risk of cancer following high, and very high, doses of ionising radiation

Proteomic Analysis of Plasma at the Preterminal Stage of Rhesus Nonhuman Primates Exposed to a Lethal Total-Body Dose of Gamma-Radiation

Proteomic analysis of plasma at the preterminal stage of rhesus nonhuman primates exposed to a lethal total-body dose of gamma-radiation

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