Targetable alterations and personalized treatment in ameloblastoma: results from a prospective observational...

Ameloblastomas are locally aggressive jaw tumors, primarily treated with radical surgery, which often results in significant functional and aesthetic morbidity. Innovative, personalized treatment strategies to reduce patient burden without compromising oncologic control remain lacking. This prospective observational study included comprehensive molecular profiling of 14 patients with ameloblastoma. Pathogenic mutations were identified in all cases, including alterations in BRAF, SMO, HRAS, FGFR2, and PIK3CA. Personalized treatment recommendations were made for 13 patients, and 11 received matched therapies: dabrafenib ± trametinib (n = 9), futibatinib (n = 1), or binimetinib (n = 1). Radiological tumor regression occurred in 10 of 11 treated patients. Four patients underwent surgery following neoadjuvant therapy, allowing for reduced resection extent and resulting in partial or complete pathological responses. These findings demonstrate frequent actionable alterations in ameloblastoma and clinically meaningful responses of targeted therapies. Incorporating precision oncology into standard care may facilitate personalized, less morbid surgery and improved outcomes in these rare tumors.