Metabolic Crosstalk Between Host and Tumor as a Circuit of Resilience in Cancer Therapy

Therapeutic resistance in cancer arises not only from intrinsic metabolic plasticity within the tumor, but also from the systemic metabolic state of the host organism. This review advances an integrated framework centered on the metabolic network between the host and tumor to examine how host-related factors-particularly aging, nutrition, and psychological stress-remodel systemic metabolism and thereby influence the efficacy of diverse cancer therapies. We highlight a bidirectional metabolic interplay: host physiology establishes a permissive context for tumor metabolic adaptation, whereas anticancer therapies, in turn, perturb host metabolic homeostasis, accelerating aging and compromising neurocognitive health. Ultimately, we propose that overcoming therapeutic resistance will require strategies that simultaneously target tumor metabolic dependencies and reprogram the host metabolic milieu-a systemic approach poised to redefine precision oncology.