title: Mitigating the risk of radiation-induced cancers: limitations and paradigms in drug development.
abstract: The United States radiation medical countermeasures (MCM) programme for radiological and nuclear incidents has been focusing on developing mitigators for the acute radiation syndrome (ARS) and delayed effects of acute radiation exposure (DEARE), and biodosimetry technologies to provide radiation dose assessments for guiding treatment. Because a nuclear accident or terrorist incident could potentially expose a large number of people to low to moderate doses of ionising radiation, and thus increase their excess lifetime cancer risk, there is an interest in developing mitigators for this purpose. This article discusses the current status, issues, and challenges regarding development of mitigators against radiation-induced cancers. The challenges of developing mitigators for ARS include: the long latency between exposure and cancer manifestation, limitations of animal models, potential side effects of the mitigator itself, potential need for long-term use, the complexity of human trials to demonstrate effectiveness, and statistical power constraints for measuring health risks (and reduction of health risks after mitigation) following relatively low radiation doses (<0.75 Gy). Nevertheless, progress in the understanding of the molecular mechanisms resulting in radiation injury, along with parallel progress in dose assessment technologies, make this an opportune, if not critical, time to invest in research strategies that result in the development of agents to lower the risk of radiation-induced cancers for populations that survive a significant radiation exposure incident.
authors.affiliation: Radiation Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Yoo
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Jorgensen
authors.forename: Ann R
authors.initials: AR
authors.lastname: Kennedy
authors.forename: John D
authors.initials: JD
authors.lastname: Boice
authors.forename: Alla
authors.initials: A
authors.lastname: Shapiro
authors.forename: Tom C-C
authors.initials: TC
authors.lastname: Hu
authors.forename: Brian R
authors.initials: BR
authors.lastname: Moyer
authors.forename: Marcy B
authors.initials: MB
authors.lastname: Grace
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Kelloff
authors.forename: Michael
authors.initials: M
authors.lastname: Fenech
authors.forename: Pataje G S
authors.initials: PG
authors.lastname: Prasanna
authors.forename: C Norman
authors.initials: CN
authors.lastname: Coleman
mesh_terms: D015195:Drug Design; D006801:Humans; D009381:Neoplasms, Radiation-Induced / Q000175:diagnosis* / Q000517:prevention & control*; D011829:Radiation Dosage; D011835:Radiation Protection / Q000379:methods*; D011837:Radiation-Protective Agents / Q000138:chemical synthesis / Q000627:therapeutic use*; D018788:Radioactive Hazard Release; D011874:Radiometry / Q000379:methods*; D018570:Risk Assessment / Q000379:methods
chemical_list: D011837:Radiation-Protective Agents
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