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Paracrine IGF1/IGF1R signaling initiated by radiotherapy-activated cancer-associated fibroblasts promotes colorectal cancer progression (Tommelein et al., 2018), and the radiation-induced secretion of IGF1 in human fibroblasts up-regulated IGF1R/Akt signaling in bystander cells (Ivanov et al., 2010)

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Proposed pathways include modulation of multiple neurotransmitter systems (influencing serotonin, dopamine, norepinephrine, GABA, glutamate levels), possible involvement of NMDA receptors, alpha-1 adrenergic signaling (e.g., potentiating pineal acetyltransferase activity), inhibition of somatostatin release via dopaminergic routes, reduced ACTH/cortisol for stress buffering, and stimulated growth hormone or somatoliberin secretion