Neural remodeling shapes a nerve-dependent metastatic ecosystem in ovarian cancer.

Ovarian cancer (OC) remains a highly lethal malignancy characterised by diffuse peritoneal dissemination and frequent treatment resistance. Beyond tumor-intrinsic alterations and classical stromal support, the peripheral nervous system is emerging as an important component of the tumor microenvironment. Here, we develop an OC-focused framework of a nerve-dependent metastatic niche, integrating tumor-associated neural remodeling, subtype-specific neural signalling and neuro-immune crosstalk across disease progression. We outline the physiological basis of ovarian and tubo-ovarian innervation and examine how OC may co-opt peripheral neural programmes through neurotrophic factors, axon-guidance molecules and extracellular vesicle signalling. Particular emphasis is placed on sensory and adrenergic pathways implicated in angiogenesis, tumor-cell survival, invasion and immune regulation, while distinguishing OC-specific evidence from mechanisms established in other malignancies. We further consider how neural responsiveness may be reconfigured during peritoneal dissemination through interactions with ascitic, adipose, immune, stromal and mechanical niches. Finally, we discuss emerging neuro-targeted strategies, including receptor antagonism, neurotransmitter-synthesis inhibition, neural manipulation and AAV-enabled neuroengineering, and highlight the translational opportunities and current limitations of targeting nerve-tumor crosstalk in OC.