Abstract 7631: Predicting and preventing cancer stemness in low Earth orbit

Abstract Cancer stemness properties, including enhanced survival, malignant regeneration, telomere deregulation, genomic and epitranscriptomic instability, fuel metastases, and have been linked to stress, retrotransposon and inflammatory cytokine activation, which can occur in low earth orbit (LEO). In NASA Axiom 1, 2 and 3 missions to the ISS, confocal imaging, WGS, RNA-seq and scRNA-seq of lentiviral FUCCI2BL cell cycle and ADAR1-GFP reporter transduced erythroleukemia (TF-1a), colorectal (Caco-2) and metastatic breast cancer (MBC; MDA-MB-231 and patient samples) revealed proliferation, significant genomic instability, HERV and LINE-1 retrotransposon deregulation, and APOBEC3C and ADAR1 activation. Moreover, in Axiom 2 and 3 missions with ADAR1-reporter expressing MBC organoids and in humanized MBC mouse models, an ADAR1p150 splicing modulator, rebecsinib (IND 153126), prevented tumor propagation. Thus, cancer studies in LEO may accelerate the development of innovative cancer therapeutics and countermeasures for long-term spaceflight. Citation Format: Jessica Pham, Wenxue Ma, Claire Engstrom, Patrick Chang, Shuvro P. Nandi, Inge van der Werf, Emma Klacking, Teresa Sposito, Kendale Wirtjes, Thomas Frias, Antonio Ruiz, Jane Isquith, Luisa Ladel, Christina N. Wu, Jana Stoudemire, Pinar Mesci, Kay T. Yeung, Rebecca A. Shatsky, Anna A. Khachatrian, James J. La Clair, Michael D. Burkart, Peggy Wentworth, Curtis L. Scribner, Sheldon R. Morris, Thomas Whisenant, Karla Mack, Ludmil B. Alexandrov, Catriona H. Jamieson. Predicting and preventing cancer stemness in low Earth orbit abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7631.