Adaptive preconditioning with low-dose radiation: translational challenges from radiobiology to radiotherapy

As a paradigm-shifting concept in radiobiology, low-dose radiation preconditioning (LDRP) describes a phenomenon wherein prior low-dose exposure engenders resistance to subsequent high-dose challenges. Although this adaptive response has been observed across diverse biological systems, its mechanistic basis, determinants of inter-individual variability, and clinical translatability remain under active investigation. This narrative review synthesizes the available evidence on LDRP, critically appraising current knowledge across three interconnected domains: (1) the molecular architecture of the adaptive response; (2) translational barriers, with emphasis on dose/dose-rate optimization, temporal intervals, and predictive biomarkers for radiotherapy; and (3) future avenues toward personalized LDRP in precision oncology. By integrating radiobiological and preclinical findings, this review offers a comprehensive framework for bench-to-bedside translation. Achieving personalized low-dose radiation strategies will hinge upon interdisciplinary collaboration, prospective validation, and the assimilation of multi-omics data into predictive algorithms— three interconnected domains that will chart the course for this emerging field.