Given current radiation-induced cancer risk estimates, long duration exploration missions will exceed permissible exposure levels set to minimize the long-term health outcomes associated with increased radiation exposure – namely the risk of exposure induced death (REID) due to cancer. While there are currently no medical countermeasures that are validated to mitigate to the long-term health effects of the chronic low dose-rate mixed field irradiation experienced in the spaceflight environment, a variety of potential countermeasures are available that can be tested in the context of space radiation exposures. FDA-approved countermeasures exist for acute radiation syndrome and tissue effects following radiotherapy, but their efficacy for these effects given space-relevant radiation exposures, safety in healthy populations, and impact on long-term health outcomes have not been well characterized. Decades of clinical cancer research have revealed effective cancer prevention, diagnostic, and treatment strategies that may be applicable in preventing, diagnosing and treating radiation-associated cancers. Countermeasures to mitigate other spaceflight-associated health outcomes are in development that may impact carcinogenesis. Nutrition and exercise have been shown impact the risk of cancer, cardiovascular and central nervous system effects in the general population. Countermeasure need to be identified that are both effective at reducing cancer risk and safe for implementation in a healthy astronaut population.

Approach

Cancer countermeasures are defined as any product or intervention that can prevent or delay carcinogenesis, provide a platform for routine, non-invasive, early detection of malignancies, or provide a pre-treatment platform for identifying particularly aggressive tumors resulting from chronic space radiation exposure. Interagency efforts and research evaluating various pharmaceuticals, dietary supplements, and nutraceuticals including anti-inflammatories and antioxidants for efficacy in mitigating radiation effects to multiple tissues are currently underway. Identification of other potential countermeasures and countermeasure screening practices will use input from advisory boards, workshop groups, national committee reports, tech watches, datamining, and computational biology. Ground-based research will assess and optimize the effectiveness and safety of countermeasures in established surrogate endpoints of radiation carcinogenesis and degenerative disease. If platforms that can support efficient screening and testing of countermeasures are not identified, these technologies will be developed (302). Drug-based countermeasures will focus on supplements, nutraceuticals, and repurposing FDA approved pharmaceuticals or FDA investigational new drugs targeting inflammation; oxidative stress; aging-related processes, or other reasonably viable surrogate endpoints of radiation carcinogenesis and degenerative disease. Non-drug based countermeasures include, but are not limited to, health outcome or biomarker surveillance and monitoring techniques, exercise regimens, dietary modification, translatable clinical cancer prevention strategies, individualized risk assessment to drive personalized medical care, etc. Countermeasure assessment needs to emphasize safety, ease-of-use, implementation in healthy populations, stability, and feasibility for long duration missions.

Drug-based countermeasures for consideration must meet the following criteria:

• Must be acceptable for use in an otherwise healthy population with consideration given to safety, risks, and benefits of possible long-term usage over the course of a mission and/or post mission timeframe.

• Benefits should clearly outweigh risks with some knowledge on potential short- and long-term side effects that may be possible at the dosages required for effective protection from space relevant exposures.

• Must have a reasonably well-understood mechanistic mode of action related to the intended space radiation induced adverse outcome.

• Must have reasonable method of administration for use in the space environment (e.g., compatible with self-administration, dosing, and required monitoring.

In addition, drug-based countermeasures for consideration will need to meet the requirements of the FDA Animal Rule to demonstrate safety and efficacy when human studies are not feasible.

• Identification of candidate countermeasures with limited to no toxicity that affect relevant biomarkers such that they may reasonably affect carcinogenic risk.

• Quantification of the effectiveness of countermeasures by high-throughput screening.