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Targeted therapies in the medical management of craniopharyngioma

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Abstract

Craniopharyngioma (CP) is an intracranial benign tumor that behaves aggressively due to its location, infiltration of the surrounding nervous tissue and high capacity for recurrence. Treatment of choice is surgery followed or not by radiotherapy. Recent advances in molecular biology techniques and the better understanding of the genetic alterations of the two histological types of CP have open new therapeutic perspectives with targeted drugs. Adamantinomatous CP (ACP) is associated with activating mutations of the CTNNB1 gene. Such mutations are accompanied by intracellular accumulation of β-catenin, an oncogenic protein that activates the intracellular Wnt/ β-catenin signaling pathway, which regulates the transcription of genes involved in cell proliferation. Therefore, the use of molecular therapies directed against the activation of the Wnt/ β-catenin pathway could be an attractive and promising therapeutic option in the management of ACPs. On the other hand, papillary CP (PCP) is associated with activating mutations in the BRAF gene. This gene encodes a BRAF protein that plays an important role in the intracellular mitogen-activated protein kinase (MAPK) signaling pathway, which also regulates cell proliferation. The use of BRAF inhibitors either in monotherapy or in combination with mitogen-activated protein kinase (MEK) inhibitors has demonstrated therapeutic efficacy in isolated clinical cases of relapsed PCPs. A preliminary report of a recent phase II clinical trial has shown a therapeutic response in 93.7% of patients with BRAF V600E -mutated PCP, with an 85% reduction in tumor size. In the present review we comment on the efficacy and safety of the different drugs being used in patients with PCP.

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  1. Department of Endocrinology, Hospital Universitario Puerta de Hierro Majadahonda, Instituto de Investigación Sanitaria Puerta de Hierro Segovia de Arana (IDIPHISA), Calle Manuel de Falla 1, 28222, Madrid, Spain

    Pedro Iglesias

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Iglesias, P. Targeted therapies in the medical management of craniopharyngioma. Pituitary 25, 383–392 (2022). https://doi.org/10.1007/s11102-022-01212-4

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