Bidirectional Neurobiological Interactions Between Cancer and PTSD: Mechanisms and Emerging Therapeutic Implications

This review aims to illustrate the bidirectional neurobiological mechanisms underlying cancer and Post-Traumatic Stress Disorder (PTSD) comorbidity, highlight the active regulatory role of the nervous system, and propose targeted intervention strategies.

This narrative review was conducted by searching PubMed, Google Scholar, and Web of Science for all years up to 2025. The following search terms were combined: "PTSD" AND "Tumor microenvironment" OR "Neural circuit" AND "cancer". Of the 1182 articles initially identified, 115 were enrolled in integrative analysis after duplicate removal, initial title/abstract screening, and overall text eligibility.

As a traumatic stressor, cancer induces PTSD via diagnostic distress, treatment-related brain structural alterations, fear circuit activation, and neuroinflammation. PTSD, in turn, increases the risk of neoplastic development by disrupting the Hypothalamic-Pituitary-Adrenal (HPA) axis, leading to hyperactivity of the Sympathetic Nervous System (SNS) and restructuring immune functions to create a pro-tumor microenvironment. Moreover, cancer cells can actively hijack neuronal functions to promote malignant progression by forming neuron-tumor synapses, internalizing neuronal mitochondria, and integrating into neural networks. The mechanisms we mentioned in the article - such as tumor synapse formation and transfer of neuronal mitochondria - mainly come from preclinical studies and have not yet obtained direct clinical evidence in humans.

Mental illness and cancer have a wide positive bidirectional relationship, which poses a challenge to the traditional dichotomy between physical illness and psychological disorders. This highlights the need to integrate mind-body treatment in the practice of oncology and psychiatry.

The nervous system is an active regulator and not a passive responder in patients with comorbid cancer and PTSD. Disruption of this pathological cycle requires the development of specific interventions that target neural signaling, metabolic crosstalk, and neuroendocrine pathways.