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Cited by 11Effects of Radiation ExposureSpaceflight effects on biologySpace exploration and regulation

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RRx-001 and the “Right stuff”: Protection and treatment in outer space

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Oronsky, Bryan, Caroen, Scott, Abrouk, Nacer, Reid, Tony R.·2022·Life Sciences in Space Research
DOI 10.1016/j.lssr.2022.05.001
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Abstract

From antibiotics to aspirin to antimalarials and to anticancer agents, about half of the world's best-selling drugs are derived from nature. However, accelerating climatic disruption, habitat destruction, pollution, and biodiversity loss all negatively impact the potential of natural sources to continue to serve as repositories of novel pharmaceuticals. On that basis, the final frontier for drug development is perhaps not the rainforests, coral reefs, and other natural habitats but rather the aerospace industry with its virtually unlimited and inexhaustible man-made 'library' of potentially bioactive compounds. The first aerospace-sourced therapeutic to reach the clinic is RRx-001, an inhibitor of the NOD-like receptor - Nucleotide-binding oligomerization domain with Leucine rich Repeat and Pyrin domain (NLRP3) inflammasome in a Phase 3 trial for the treatment of small cell lung cancer (SCLC) and in a soon-to-start Phase 3 trial for protection against chemoradiotherapy-induced severe oral mucositis in first line head and neck cancer. As manned missions to the Moon, Mars, and asteroids as well as space tourism beckon, it is perhaps fitting that a compound like RRx-001, which is derived from 1,3,3-Trinitroazetidine (TNAZ), an explosive propellant for rockets, is a potential "all purpose" option to mitigate the major biomedical effects of space radiation exposures including cancer development and other tissue degenerations both within mission and after mission. This article highlights the promise of RRx-001 to attenuate the acute and late effects of radiation exposure on astronauts including the development of cancer.

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Research works printed but not linked: 48

  1. Institute of Medicine (US) Committee on creating a vision for space medicine during travel beyond earth orbit; Ball JR, Evans CH Jr., editors. Safe Passage: Astronaut Care For Exploration Missions. Washington (DC): National Academies Press (US); 2001. 3, Managing Risks to Astronaut Health. Available from: https://www.ncbi.nlm.nih.gov/books/NBK223777/.
  2. Berliner, 2021, Towards a biomanufactory on mars, Perspective article Front. Astron. Space Sci., 8, 120
  3. Blue, 2019, Supplying a pharmacy for NASA exploration spaceflight: challenges and current understanding, npj Microgravity, 5, 14, 10.1038/s41526-019-0075-2 · DOI · Paper page
  4. Bonomi, 2020, J. Clin. Oncol., 38, 12081, 10.1200/JCO.2020.38.15_suppl.12081 · DOI
  5. Brouse, 2015, Impact of hemoglobin nitrite to nitric oxide reductase on blood transfusion for resuscitation from hemorrhagic shock, Asian J. Transfus. Sci, 9, 55, 10.4103/0973-6247.150952 · DOI
  6. Cabrales, 2017, The macrophage stimulating anti-cancer agent, RRx-001, protects against ischemia-reperfusion injury, Expert Rev. Hematol., 10, 575, 10.1080/17474086.2017.1324779 · DOI
  7. Caroen, 2020, Rationale and necessity for delivery of RRx-001, a Myc and CD47 antagonist, by intravenous blood mix, Expert Opin. Drug Deliv., 17, 741, 10.1080/17425247.2020.1761787 · DOI
  8. Chatterjee, 2019, LGM2605 reduces space radiation-induced NLRP3 inflammasome activation and damage in in vitro lung vascular networks, Int. J. Mol. Sci, 20, 176, 10.3390/ijms20010176 · DOI
  9. Chen, 2019, Severe acute respiratory syndrome coronavirus viroporin 3a activates the NLRP3 inflammasome, Front. Microbiol., 10, 50, 10.3389/fmicb.2019.00050 · DOI
  10. Chen, 2021, Rrx-001 ameliorates inflammatory diseases by acting as a potent covalent NLRP3 inhibitor, Cell. Mol. Immunol., 18, 1425, 10.1038/s41423-021-00683-y · DOI
  11. Corcoran, 2021, Pharmacological inhibition of the nod-like receptor family pyrin domain containing 3 inflammasome with MCC950, Pharmacol. Rev, 73, 968, 10.1124/pharmrev.120.000171 · DOI
  12. Cortese, 2018, Vive la radiorésistance!: converging research in radiobiology and biogerontology to enhance human radioresistance for deep space exploration and colonization, Oncotarget, 9, 14692, 10.18632/oncotarget.24461 · DOI · Paper page
  13. Criscuolo, 2019, New combinatorial strategies to improve the PARP inhibitors efficacy in the urothelial bladder cancer treatment, J. Exp. Clin. Cancer Res., 38, 91, 10.1186/s13046-019-1089-z · DOI
  14. Ding, 2020, Natural products that target the NLRP3 inflammasome to treat fibrosis, Front. Pharmacol., 11, 10.3389/fphar.2020.591393 · DOI
  15. El-Sharkawy, 2020, Inhibiting the NLRP3 inflammasome, Molecules, 25, 5533, 10.3390/molecules25235533 · DOI
  16. Fens, 2016, Targeting tumor hypoxia with the epigenetic anticancer agent, RRx-001: a superagonist of nitric oxide generation, Med. Oncol., 33, 85, 10.1007/s12032-016-0798-9 · DOI
  17. Furukawa, 2020, Space radiation biology for “Living in space”, Biomed. Res. Int., 2020, 10.1155/2020/4703286 · DOI
  18. Huang, 2020, The role of NLRP3 inflammasome in radiation-induced cardiovascular injury, Front. Cell Dev. Biol., 8, 140, 10.3389/fcell.2020.00140 · DOI
  19. Jurgensen, 2018, Characterizing the radioprotective effects of RRx-001 utilizing an in vitro model, Radiat. Res. Soc
  20. Jurgensen, 2021, RRx-001 radioprotection: enhancement of survival and hematopoietic recovery in gamma-irradiated mice, Front. Pharmacol., 12, 10.3389/fphar.2021.676396 · DOI
  21. Kennedy, 2014, Acute effects of solar particle event radiation, J. Radiat. Res., 55, 10.1093/jrr/rrt196 · DOI
  22. King, 2020, Use of amifostine for cytoprotection during radiation therapy: a review, Oncology, 98, 61, 10.1159/000502979 · DOI
  23. Levchenko, 2018, Mars colonization: beyond getting there, Glob. Chall., 3
  24. Ma, 2021, Inhibition of the inflammasome activity of NLRP3 attenuates HDM-induced allergic asthma, Front. Immunol., 12, 10.3389/fimmu.2021.718779 · DOI
  25. Monje, 2003, Farming in space: environmental and biophysical concerns, Adv. Space Res., 31, 151, 10.1016/S0273-1177(02)00751-2 · DOI
  26. Montesinos, 2021, Space radiation protection countermeasures in microgravity and planetary exploration, Life (Basel), 11, 829
  27. Morra, 2019, CCDC6 and USP7 expression levels suggest novel treatment options in high-grade urothelial bladder cancer, J. Exp. Clin. Cancer Res., 38, 90, 10.1186/s13046-019-1087-1 · DOI
  28. Ning, 2012, Dinitroazetidines are a novel class of anticancer agents and hypoxia-activated radiation sensitizers developed from highly energetic materials, Cancer Res., 72, 2600, 10.1158/0008-5472.CAN-11-2303 · DOI
  29. Ning, 2018, Pilot study of the antitumor efficacy and tolerability of orally administered RRx-001 in normal and tumor-bearing mice, J. Cancer Res. Therap. Oncol., 4, 1
  30. Ning, 2015, Nrf2 activity as a potential biomarker for the pan-epigenetic anticancer agent, RRx-001, Oncotarget, 6, 21547, 10.18632/oncotarget.4249 · DOI
  31. O’D Alexander, 2018, Water reservoirs in small planetary bodies: meteorites, asteroids, and comets, Space Sci. Rev., 214, 36, 10.1007/s11214-018-0474-9 · DOI
  32. Oronsky, 2021, RRx-001, a downregulator of the CD47- SIRPα checkpoint pathway, does not cause anemia or thrombocytopenia, Expert Opin. Drug Metab. Toxicol., 17, 355, 10.1080/17425255.2021.1876025 · DOI
  33. Oronsky, 2018, A review of clinical radioprotection and chemoprotection for oral mucositis, Transl. Oncol., 11, 771, 10.1016/j.tranon.2018.03.014 · DOI
  34. Oronsky, 2020, Desperate times, desperate measures: the case for RRx-001 in the treatment of COVID-19, Semin. Oncol., 47, 305, 10.1053/j.seminoncol.2020.07.002 · DOI
  35. Oronsky, 2019, REPLATINUM phase III randomized study: rRx-001 + platinum doublet versus platinum doublet in third-line small cell lung cancer, Future Oncol., 15, 3427, 10.2217/fon-2019-0317 · DOI
  36. Oronsky, 2016, RRx-001, a novel dinitroazetidine radiosensitizer, Investig. New Drugs, 34, 371, 10.1007/s10637-016-0326-y · DOI
  37. Oronsky, 2012, The scarlet letter of alkylation: a mini review of selective alkylating agents, Transl. Oncol., 5, 226, 10.1593/tlo.12187 · DOI
  38. Reid, 2015, Safety and activity of RRx-001 in patients with advanced cancer: a first-in-human, open-label, dose-escalation phase 1 study, Lancet Oncol., 16, 1133, 10.1016/S1470-2045(15)00089-3 · DOI
  39. Scicinski, 2014, Development of methods for the bioanalysis of RRx-001 and metabolites, Bioanalysis, 6, 947, 10.4155/bio.13.331 · DOI
  40. Scicinski, 2015, NO to cancer: the complex and multifaceted role of nitric oxide and the epigenetic nitric oxide donor, RRx-001, Redox Biol., 6, 1, 10.1016/j.redox.2015.07.002 · DOI
  41. Scicinski, 2012, Preclinical evaluation of the metabolism and disposition of RRx-001, a novel investigative anticancer agent, Drug Metab. Dispos., 40, 1810, 10.1124/dmd.112.046755 · DOI
  42. Setlow, 2003, The hazards of space travel, EMBO Rep., 4, 1013, 10.1038/sj.embor.7400016 · DOI
  43. Sher, 2020, Results of a randomized, open label, multicenter trial assessing the safety, dose and schedule of RRx-001 (R001) in reducing severe oral mucositis (SOM) in patients receiving chemoradiation (CRT) for oral cavity/oropharynx squamous cell carcinoma (OSCC), Int. J. Radiat. Oncol., 108, 10.1016/j.ijrobp.2020.07.2291 · DOI
  44. Simon, 2021, Stability of antimicrobial drug molecules in different gravitational and radiation conditions in view of applications during outer space missions, Molecules, 26, 2221, 10.3390/molecules26082221 · DOI
  45. Singh, 2018, Opportunities and challenges with animal models for acute radiation syndrome drug discovery, Expert Opin. Drug Discov., 1
  46. von Braun W, Ryan C. Can we get to MARS? Collier's. April 30, 1954 pp. 22-29.
  47. Yalcin, 2015, From METS to malaria: rRx-001, a multi-faceted anticancer agent with activity in cerebral malaria, Malar. J., 14, 218, 10.1186/s12936-015-0720-5 · DOI
  48. Zhao, 2015, Epigenetic effects of RRx-001: a possible unifying mechanism of anticancer activity, Oncotarget, 6, 43172, 10.18632/oncotarget.6526 · DOI

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Metadata

Authors
Oronsky, B., Caroen, S., Abrouk, N., & Reid, T. R.
Affiliations
EpicentRx, Inc. (United States) (US)
Corresponding author
Oronsky, Bryan
ORCID
Venue
Life Sciences in Space Research
Publisher
Elsevier BV
Published
2022-11
Volume
35
Pages
69-75
ISSN
2214-5524 (ISSN-L)
DOI
10.1016/j.lssr.2022.05.001
OpenAlex
W4280618760
Cited by
11
References
3
Citations by year
2025: 1 · 2024: 1 · 2023: 8 · 2022: 1
FWCI
1.57
Type
journal article
Language
en
Open access
Licence
Locations
  • Life Sciences in Space Research (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
  • Health Sciences › Medicine › Physiology (medical) › Spaceflight effects on biology
  • Social Sciences › Political Science and International Relations › Space exploration and regulation
Keywords
RRx-001, NLRP3 inhibitors, 1,3,3-trinitroazetidine, space radiation, radiation-induced cancer, small cell lung cancer, head and neck cancer, oral mucositis, chemoradiotherapy, astronaut health, space medicine, drug discovery
MeSH terms
Azetidines, Extraterrestrial Environment, Humans, Neoplasms, Nitro Compounds, Space Flight, Clinical Trials, Phase III as Topic, Astronauts

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