Decoding craniopharyngioma: From mechanisms to therapy.
Jose Mario Gonzalez-Meljem1, Lei Cao2, John Richard Apps3
1Tecnologico de Monterrey, School of Engineering and Sciences, Mexico City, Mexico.
Best Practice & Research. Clinical Endocrinology & Metabolism
|October 12, 2025
Summary
Recent craniopharyngioma research decodes subtypes, revealing senescence-driven pathogenesis in adamantinomatous craniopharyngioma (ACP) and BRAF mutations in papillary craniopharyngioma (PCP). This advances targeted therapies for improved patient outcomes.
Area of Science:
- Neuro-oncology
- Molecular biology
- Tumor microenvironment research
Background:
- Craniopharyngioma is a complex sellar tumor with distinct subtypes.
- Recent research has elucidated the genetic drivers and pathogenesis of these subtypes.
Purpose of the Study:
- To summarize recent advancements in understanding craniopharyngioma subtypes.
- To highlight the translation of these findings into novel therapeutic strategies.
Main Methods:
- Genetic and histological subtyping (adamantinomatous craniopharyngioma [ACP] and papillary craniopharyngioma [PCP]).
- Development of ACP mouse models and human studies.
- Single-cell RNA sequencing to analyze tumor ecosystems.
Main Results:
- ACP is linked to CTNNB1 mutations and WNT pathway activation.
- PCP is characterized by BRAF-V600E mutations.
- Senescence-driven pathogenesis in ACP involves paracrine signaling, creating a tumor-promoting microenvironment.
Conclusions:
- Foundational insights into craniopharyngioma biology are paving the way for targeted therapies.
- BRAF/MEK inhibitors for PCP and senescence-associated secretory phenotype (SASP) inhibitors for ACP show therapeutic promise.
