Targeted treatment for craniopharyngioma.

Introduction: Craniopharyngioma is a rare solid-cystic tumor of the hypothalamopituitary region. Two distinct craniopharyngioma types (formerly subtypes), adamantinomatous and papillary, have been described. These tumors often manifest with neuroendocrine dysfunction, vision problems, hydrocephalus, and cognitive changes. Despite efforts to spare vital brain structures, conventional treatments such as surgery and radiation can exacerbate preceding deficits and contribute to permanent neurologic impairment. Recent studies have identified BRAF-V600E mutations in nearly all papillary craniopharyngiomas (PCP), and CTNNB1/Wnt pathway alterations in adamantinomatous craniopharyngiomas (ACP). These discoveries have advanced our understanding of craniopharyngioma pathogenesis and have opened opportunities for targeted biological treatments.

Purpose: The primary objective of this article is to review the current landscape of targeted treatments in papillary and adamantinomatous craniopharyngioma.

Results: Treatment of PCP with BRAF/MEK inhibition has demonstrated durable tumor response in the adjuvant and neoadjuvant settings in multiple case studies and one phase II clinical trial. Although treatment advances are more limited for ACP, CTNNB1/Wnt pathway inhibitors showed promising results in pre-clinical studies and are under continued investigation.

Conclusion: The efficacy of BRAF/MEK inhibition in PCP supports the use of targeted therapy in patients with newly diagnosed PCP. The optimal targeted treatment combinations and their timing, duration, long-term effects, and sequencing with traditional therapeutic modalities have not been established and warrant further study. Targeted therapies represent a significant advancement in the field of oncology, and craniopharyngiomas are viable candidates for these approaches pending further research.