Although established approaches along with new surgical and radiotherapeutic approaches remain the main treatment modalities, recent evidence has provided insight into their molecular pathogenesis involving, other than chemotherapy, treatments with targeted agents as in gliomas and craniopharyngiomas bearing BRAF mutations.
In conclusion, mutation profiles of BRAF wild-type craniopharyngiomas and ameloblastomas share mutations of FGFR genes and have additional mutations with potential for targeted therapy.
A thorough analysis of the alterations of β-catenin/CTNNB1 and BRAF genes investigated in 1123 CP cases included in 27 studies, showed that, on average, CTNNB1 mutations were present in two-thirds of adamantinomatous CPs and BRAF mutations in 90% of papillary CPs.
Papillary craniopharyngiomas are defined by BRAF <sup>V600E</sup> mutations while β-catenin alterations characterize adamantinomatous craniopharyngiomas.
In total, 14-50% of adult-onset craniopharyngioma are papillary; the majority with a mutation in exon 3 of BRAF and may respond to BRAF inhibitors and mitogen-activated protein kinase inhibitors.
As these targetable mutations warrant prospective research, the authors will be conducting a national National Cancer Institute-sponsored multicenter clinical trial to investigate BRAF/MEK inhibition in the treatment of craniopharyngioma.
Here, we describe our treatment of a man age 39 years with multiply recurrent BRAFV600Ecraniopharyngioma using dabrafenib (150mg, orally twice daily) and trametinib (2mg, orally twice daily).
Targeted genotyping revealed BRAFp.Val600Glu in 95% of papillary craniopharyngiomas (36 of 39 tumors) and mutation of CTNNB1 in 96% of adamantinomatous craniopharyngiomas (51 of 53 tumors).