Thirty years of NCI thyroid cancer research investment (1996-2025): a longitudinal portfolio analysis of funding trends, molecular target emphasis and thematic evolution.

BACKGROUND: Thyroid cancer research has shifted over the past three decades toward molecular classification, precision diagnostics and targeted therapy. However, the evolution of public research investment in this field has not been systematically characterized. This study analyzed National Cancer Institute (NCI)-administered thyroid cancer research funding from 1996 to 2025. METHODS: We performed a longitudinal portfolio analysis of NIH RePORTER records from fiscal years 1996-2025. NCI-administered projects with explicit thyroid cancer research relevance were identified through review of project titles, abstracts, public health relevance statements and project terms. The final analytic cohort comprised 753 project-award years (AYs). Rule-based dictionaries were used to annotate research stage, disease subtype, molecular target and therapeutic or diagnostic modality. Deduplicated project text was further analyzed using MedCPT biomedical embeddings and BERTopic to identify higher-order thematic domains. RESULTS: The cohort represented approximately USD 343.8 million in cumulative NCI funding in BRDPI-adjusted 2025 U.S. dollars. Annual research activity increased over time, peaking in 2015 with 53 active AYs and approximately USD 24.8 million in BRDPI-adjusted 2025 U.S. dollars. Translational or mixed clinical-preclinical research accounted for the largest share of the portfolio (46.5%), and R01 awards were the dominant funding mechanism (48.5%). Papillary thyroid carcinoma was the most frequently annotated subtype, followed by anaplastic, differentiated, follicular, poorly differentiated and medullary thyroid cancers. BRAF, RET, MAPK/MEK, PI3K/AKT/mTOR and RAS were the leading molecular targets. Topic modelling identified five higher-order thematic domains, suggesting a relative shift from broad thyroid cancer characterization toward diagnosis and risk stratification, molecular signaling, treatment-response biology and therapeutics for aggressive or advanced disease. CONCLUSIONS: NCI-administered thyroid cancer research funding expanded between 1996 and 2025 and became increasingly translational, molecularly informed and clinically oriented. These findings provide an empirical map of public research investment in thyroid oncology and may help inform future funding priorities.