From pathogenesis to precision medicine: Transformative advances in research and treatment of ameloblastoma

Odontogenic neoplasms of the jaw are dominated by ameloblastoma (AM), a locally aggressive epithelial tumor with a significant propensity for recurrence. The World Health Organization's 2022 update to the AM classification system underscores recent progress in comprehending its underlying mechanisms and refining clinical approaches. Contemporary research has yielded significant insights into the genetic underpinnings of AM, paving the way for the development of precision-based treatment strategies. Advanced genetic profiling has revealed a significant frequency of BRAF (V-raf murine sarcoma viral oncogene homolog) V600E and SMO (Smoothened) gene alterations in AM. Importantly, therapeutic interventions specifically designed to target these genetic aberrations, including BRAF and MEK pathway blockers, have shown encouraging results in terms of both effectiveness and tolerability, as documented in individual case reports and small-scale clinical investigations. This comprehensive review summarizes the recent modifications to the World Health Organization's categorization of AMs, explores progress in elucidating their underlying molecular pathways, and evaluates emerging targeted treatment modalities. Our objective is to present a thorough synthesis of contemporary scientific discoveries and therapeutic interventions, potentially paving the way for more efficacious and individualized clinical management protocols for this complex neoplasm.