Gap Cancer-304: Identify and/or develop strategies for accelerated countermeasure development.
Last Published:  07/30/21 01:05:31 PM (Central)
Responsible Element: Space Radiation (SR)
Status: Open
Description

Strategies to develop countermeasures against terrestrial radiation exposure typically revolve around agents either that 1) alter the physical interactions of normal tissues to direct exposure (i.e., scavenging the reactive oxygen species generated by the radiolysis of water) or 2) mitigate the downstream biological processes following exposure (i.e., reducing the radiation-induced inflammatory response). Clinical radioprotectors are administered before a planned therapeutic exposure(s) to reduce the likelihood and severity of undesirable side effects. To date, Amifostine is the only FDA-approved radioprotector, but the potential side effects, including severe anaphylactic reactions, reduce the operational utility for spaceflight.  Radiomitigators are given following and unexpected exposure such as a terrorist attack or an accidental occupational exposure. Space radiation exposures differ from terrestrial exposures both in the type of radiation experienced and the rates at which those exposures occur. The quality and dose rate of radiation experienced in the deep space environment present unique challenges in terms of replicating them on the ground, estimating health risks from such exposures and developing strategies to counteract those risks. Traditional in vivo strategies to assess interventional countermeasure efficacy require long-term follow up and large animal cohorts, which limit feasible throughput. Time and resource constraints limit the number of compounds that can be tested using these strategies prior to a Mars mission where the exposure to space radiation exceeds NASA’s permissible exposure limits (PELs). Therefore, strategies that accelerate countermeasure identification, prioritization, and validation need to be developed to improve likelihood of success.

Approach

Ground-based research to determine the most appropriate surrogate endpoints that best predict countermeasure effectiveness. New high-throughput screening and informatics technologies to pursue large-scale agnostic countermeasure identification in combination with more targeted, informational approaches represent an attractive comprehensive strategy. These approaches would require the identification of surrogate biomarkers for initiation of carcinogenesis that could confidently predict tumorigenesis in models appropriate for this “big science” approach. Therefore, the identification of surrogate biological endpoints that rapidly and accurately predict carcinogenic outcomes and can be adapted for use in high-throughput screening and informatics platforms are necessary.

Target for Closure
  • Development of countermeasure screening and testing platforms using likely surrogate endpoints.
Mappings
Risk Risk of Radiation Carcinogenesis
You are here! Gap Cancer-304: Identify and/or develop strategies for accelerated countermeasure development.

Multi-Disciplinary Research Plans

Documentation:
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