Brain-derived neurotrophic factor in gynecological cancers and endometriosis: A candidate biomarker for diagnosis and disease monitoring

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, has functions beyond neuronal survival and synaptic plasticity, including the regulation of cellular proliferation, migration, angiogenesis, inflammation, and nociceptive signaling. Growing evidence suggests that abnormal BDNF expression and dysregulated BDNF/TrkB signaling may contribute to the development and progression of gynecological malignancies, including ovarian, cervical, and endometrial cancers, as well as endometriosis. In cancer, BDNF has been associated with epithelial-mesenchymal transition, anoikis resistance, metastatic spread, and therapeutic resistance through PI3K/Akt, MAPK/ERK, and PLCγ signaling. In endometriosis, increased circulating and tissue BDNF has been associated with neuroangiogenesis, pelvic pain, lesion severity, and inflammatory remodeling. Emerging clinical and translational evidence suggests that BDNF may have potential as a minimally invasive biomarker, mainly in endometriosis, whereas clinical data in gynecological cancers come largely from tissue expression studies; however, associations between circulating BDNF levels and disease presence, severity, or treatment response remain heterogeneous across studies. The review is based on searches of PubMed/MEDLINE, Scopus, and Web of Science from database inception to June 2025. This review critically synthesizes the molecular mechanisms underlying BDNF dysregulation and its interactions with hormonal, immune, and epigenetic pathways, while evaluating its potential clinical utility for diagnosis and disease monitoring. Particular emphasis is placed on methodological limitations, contradictory findings, and factors that may contribute to variability among studies. Key knowledge gaps and future research priorities, including standardized measurement approaches, prospective investigations, and independent cohort validation, are also discussed. Overall, current evidence supports further investigation of BDNF as a candidate biomarker, but its diagnostic and disease-monitoring utility has not been established and requires prospective clinical validation.