Cancer therapy-related cognitive impairment, part 1: an integrative clinical–mechanistic framework from phenotypes to convergent neurobiological pathways

Abstract Cancer therapy-related cognitive impairment (CRCI) is a frequent complication of cancer treatment. It involves multiple biological mechanisms: neuroinflammation, oxidative stress, mitochondrial dysfunction, impaired neurogenesis, and altered brain connectivity. Although these mechanisms have been extensively studied, evidence across cytotoxic chemotherapy, endocrine therapy, and targeted therapies is often presented separately. This review is the first of a two-part series addressing the mechanisms underlying CRCI and current and emerging therapeutic strategies for its prevention and management. It integrates available clinical and mechanistic research results across treatment classes, highlighting shared biological pathways, biomarkers, neuroimaging findings, and objective versus subjective cognitive outcomes to provide a comprehensive overview of CRCI.