Integrating polyphenols and exercise in cancer prevention, treatment, and rehabilitation: cellular and molecular mechanisms linking the injury–recovery–musculoskeletal resilience axis

Cancer progression, therapeutic interventions, and rehabilitation profoundly affect musculoskeletal integrity, impair tissue resilience, and compromise recovery, leading to functional decline and reduced quality of life. Increasing evidence suggests that combining exercise with polyphenol supplementation exerts synergistic effects in preventing tissue injury, mitigating treatment-related damage, and promoting functional recovery. This review integrates current findings on the cellular and molecular mechanisms by which polyphenols such as curcumin, resveratrol, quercetin, and green tea catechins, modulate oxidative stress, inflammation, apoptosis, autophagy, and anabolic signaling in muscle, bone, and cardiac tissues. Exercise induces mechanical loading and metabolic adaptations that activate PI3K/Akt/mTOR, MAPK/ERK, AMPK, and Nrf2 pathways, enhancing protein synthesis, mitochondrial biogenesis, and redox-adaptive capacity. Polyphenols further reinforce these effects by suppressing NF-κB and pro-inflammatory cytokines, modulating BDNF/CREB in the nervous system, and attenuating chemotherapy- or radiotherapy-induced tissue damage. Together, these interventions support musculoskeletal resilience, accelerate recovery, and optimize rey -30habilitation outcomes. By elucidating these mechanistic pathways, this review provides a framework for evidence-based integrative strategies to enhance functional preservation and repair in cancer prevention, treatment, and rehabilitation.