====== Dabrafenib ======

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Dabrafenib is a medication used in the treatment of certain types of cancers, specifically melanoma with a BRAF V600E mutation. It is an oral kinase inhibitor that targets a mutated form of the BRAF protein.

Here are some key points about Dabrafenib:

Target: Dabrafenib is designed to inhibit the activity of the BRAF protein, specifically targeting the mutated BRAF V600E form. BRAF is a protein involved in cell signaling pathways that regulate cell growth and division.

Indications: Dabrafenib is primarily used in the treatment of unresectable or metastatic melanoma (skin cancer) with a BRAF V600E mutation. It is often used in combination with another drug called trametinib, which targets MEK, another protein in the same signaling pathway.

Mechanism of Action: By inhibiting the mutated BRAF protein, Dabrafenib disrupts the signaling cascade that promotes cell growth and division. This interference is particularly important in cancer cells with the BRAF V600E mutation, as this mutation can lead to uncontrolled cell growth.

Combination Therapy: Dabrafenib is commonly used in combination with trametinib in the treatment of BRAF-mutated melanoma. This combination therapy helps to enhance the effectiveness of BRAF inhibition and reduce the likelihood of resistance development.

Adverse Effects: Like many targeted therapies, Dabrafenib can have side effects. Common side effects include fever, fatigue, rash, nausea, and joint pain. It's essential for patients to discuss potential side effects with their healthcare providers.

Monitoring: Patients receiving Dabrafenib therapy may undergo regular monitoring to assess treatment response and manage potential side effects.

It's important to note that Dabrafenib is just one component of the evolving landscape of targeted therapies for cancer treatment. Patients should consult with their healthcare providers to determine the most appropriate treatment plan based on their specific cancer type, genetic mutations, and overall health.
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An 11-year-old boy, who was diagnosed with LCH 7 years previously, presented with multiple giant intracranial lesions. At the time of his initial diagnosis, only one intracranial lesion was observed, and it began to enlarge. Currently, up to 7 intracranial lesions can be observed in this patient. However, the diagnosis of ECD was not confirmed until this most recent open resection. The BRAF V600E mutation was detected in both LCH and ECD lesions. Dabrafenib therapy exhibited dramatic efficacy in this pediatric patient. This case represents the first successful application of dabrafenib in a pediatric patient with intracranial ECD lesions as well as mixed ECD and LCH. In this article, the authors describe the intricate diagnosis and treatment processes in this patient. Recent studies regarding treatment with BRAF inhibitors for neurological involvement in mixed ECD and LCH are also reviewed
((Hao X, Feng R, Bi Y, Liu Y, Li C, Lu T, Tian Y. Dramatic efficacy of
dabrafenib in Erdheim-Chester disease (ECD): a pediatric patient with multiple
large intracranial ECD lesions hidden by refractory Langerhans cell
histiocytosis. J Neurosurg Pediatr. 2018 Sep 28:1-6. doi:
10.3171/2018.6.PEDS17728. [Epub ahead of print] PubMed PMID: 30265230.
)).

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While [[dabrafenib]] has demonstrated comparable efficacy to [[vemurafenib]] in [[BRAF V600E]] mutant melanoma patients, the BREAK-MB and dabrafenib/trametinib studies have taken BRAF inhibitor strategies further with evidence of disease activity in patients with metastatic melanoma brain metastases and potential abrogation of BRAF inhibitor resistance
((Gibney GT, Zager JS. Clinical development of dabrafenib in BRAF mutant
melanoma and other malignancies. Expert Opin Drug Metab Toxicol. 2013
Jul;9(7):893-9. doi: 10.1517/17425255.2013.794220. Epub 2013 Apr 29. Review.
PubMed PMID: 23621583.
)).

===== Dabrafenib for glioma =====

BRAFV600E mutations have been identified in several glioma subtypes, most frequently in pleomorphic xanthoastrocytoma, ganglioglioma, pilocytic astrocytoma, and epithelioid glioblastoma. Although the development of BRAF inhibitors has dramatically improved the clinical outcome for patients with BRAFV600E mutant tumors, resistance develops in a majority of patients due to the reactivation of the MAPK pathway. The addition of MEK inhibition to BRAF inhibition improves survival. 
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Dabrafenib and trametinib demonstrate promising anti-tumor efficacy in gliomas, particularly low-grade tumors, achieving durable disease stabilization in many patients. However, toxicity significantly limited tolerability. Additional research should further examine efficacy and refine safe administration protocols across glioma subtypes
((Habibi MA, Mirjani MS, Ahmadvand MH, Delbari P, Alasti O. The safety and efficacy of dabrafenib and trametinib in patients with glioma: A systematic review and meta-analysis. Eur J Clin Pharmacol. 2024 Feb 12. doi: 10.1007/s00228-024-03635-3. Epub ahead of print. PMID: 38345637.))
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Brown et al. report the successful treatment of two patients with BRAFV600E mutant pleomorphic xanthoastrocytoma using the BRAF inhibitor dabrafenib in combination with the MEK inhibitor [[trametinib]]
((Brown NF, Carter T, Kitchen N, Mulholland P. Dabrafenib and trametinib in
BRAFV600E mutated glioma. CNS Oncol. 2017 Oct 6. doi: 10.2217/cns-2017-0006.
[Epub ahead of print] PubMed PMID: 28984141.
)).