Craniopharyngioma Pathogenesis and Implications for Medical Management

Craniopharyngiomas are amongst the most challenging intracranial tumors to manage because of their invasive patterns of growth, associated morbidities, and high recurrence rate. Radiotherapy and limited chemotherapy currently serve as primary adjuvant options, but many cases remain refractory to these therapies. We review recent advances in the understanding of craniopharyngioma tumorigenesis and new targeted pharmacotherapy options for these tumors.

Papillary craniopharyngiomas demonstrate a high incidence of BRAF V600E mutation, leading to overactive B-Raf signaling. This oncogenic mutation is well-characterized in melanoma and other tumors. Targeted inhibition of B-Raf in malignant melanoma has led to improved mortality in malignant melanoma and has demonstrated efficacy in recent case reports of papillary craniopharyngioma.

Adamantinomatous craniopharyngiomas are characterized by altered β-catenin activity and disruptions in multiple growth factor signaling axes, extracellular matrix regulation, and immune microenvironment. Paracrine signaling by pituitary stem cells may also contribute to tumorigenesis. Recent development of an adamantinomatous craniopharyngioma mouse model may aid in testing promising pharmacologic therapies and biological pathways to tumorigenesis. Expanding knowledge of the biological underpinnings of craniopharyngioma will continue to drive development of targeted therapies and immunotherapies to manage this challenging disease.