Targeted therapies in the medical management of craniopharyngioma.
Pedro IglesiasPublished in: Pituitary (2022)
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.
Keyphrases
- cell proliferation
- signaling pathway
- pi k akt
- phase ii
- clinical trial
- genome wide
- copy number
- open label
- wild type
- metastatic colorectal cancer
- minimally invasive
- epithelial mesenchymal transition
- cell cycle
- healthcare
- genome wide identification
- transcription factor
- stem cells
- acute myeloid leukemia
- early stage
- randomized controlled trial
- dna methylation
- protein kinase
- double blind
- squamous cell carcinoma
- oxidative stress
- phase iii
- cancer therapy
- radiation therapy
- gene expression
- locally advanced
- study protocol
- combination therapy
- percutaneous coronary intervention
- single molecule
- multiple myeloma
- smoking cessation