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Article: Regression of BRAFV600E mutant adult glioblastoma after primary combined BRAF-MEK inhibitor targeted therapy: a report of two cases

TitleRegression of BRAFV600E mutant adult glioblastoma after primary combined BRAF-MEK inhibitor targeted therapy: a report of two cases
Authors
KeywordsBRAF-MEK inhibitors
BRAFV600E mutation
glioblastoma
targeted therapies
Issue Date2019
PublisherImpact Journals LLC. The Journal's web site is located at http://www.impactjournals.com/oncotarget/index.html
Citation
Oncotarget, 2019, v. 10 n. 38, p. 3818-3826 How to Cite?
AbstractBackground: Up to 15% of young adults with glioblastoma have the activating oncogenic BRAFV600E mutation, an actionable target of the MAPK signal transduction pathway governing tumor cell proliferation. Small molecule inhibitors of BRAF and MEK, a downstream protein immediately following BRAF, have been shown to confer a survival advantage for patients with BRAFV600E mutant advanced melanoma. We describe our experience using this combined target therapy for two patients with BRAFV600E mutant glioblastoma (GBM) as primary treatment due to extenuating clinical circumstances that prohibited the prescription of standard treatment. Case Presentation: The two patients were both 22 years old on presentation. After the initial tumor resection, they both developed rapid deterioration in performance status within a few weeks due to leptomeningeal metastases. In view of the critical condition, BRAF and MEK inhibitors were prescribed as first line treatment. The two patients both achieved dramatic clinical response, which was parallel to the impressive radiological regression of the disease. Unfortunately, the duration of disease control was short as drug resistance developed rapidly. The two patients died 7 and 7.5 month after initial diagnosis of GBM. Conclusions: Primary treatment with inhibitors of BRAF and MEK can lead to tumor regression for patients with BRAFV600E mutant glioblastoma. We therefore recommend that all young GBM patients should undergo BRAFV600E mutation testing, especially for those with unusual aggressive clinical course.
Persistent Identifierhttp://hdl.handle.net/10722/271416
ISSN
2015 Impact Factor: 5.008
2015 SCImago Journal Rankings: 2.294
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorWoo, PYM-
dc.contributor.authorLam, TC-
dc.contributor.authorPu, JKS-
dc.contributor.authorLi, LF-
dc.contributor.authorLeung, RCY-
dc.contributor.authorHo, JMK-
dc.contributor.authorZhung, JTF-
dc.contributor.authorWong, B-
dc.contributor.authorChan, TSK-
dc.contributor.authorLoong, HHF-
dc.contributor.authorNg, HK-
dc.date.accessioned2019-06-24T01:09:28Z-
dc.date.available2019-06-24T01:09:28Z-
dc.date.issued2019-
dc.identifier.citationOncotarget, 2019, v. 10 n. 38, p. 3818-3826-
dc.identifier.issn1949-2553-
dc.identifier.urihttp://hdl.handle.net/10722/271416-
dc.description.abstractBackground: Up to 15% of young adults with glioblastoma have the activating oncogenic BRAFV600E mutation, an actionable target of the MAPK signal transduction pathway governing tumor cell proliferation. Small molecule inhibitors of BRAF and MEK, a downstream protein immediately following BRAF, have been shown to confer a survival advantage for patients with BRAFV600E mutant advanced melanoma. We describe our experience using this combined target therapy for two patients with BRAFV600E mutant glioblastoma (GBM) as primary treatment due to extenuating clinical circumstances that prohibited the prescription of standard treatment. Case Presentation: The two patients were both 22 years old on presentation. After the initial tumor resection, they both developed rapid deterioration in performance status within a few weeks due to leptomeningeal metastases. In view of the critical condition, BRAF and MEK inhibitors were prescribed as first line treatment. The two patients both achieved dramatic clinical response, which was parallel to the impressive radiological regression of the disease. Unfortunately, the duration of disease control was short as drug resistance developed rapidly. The two patients died 7 and 7.5 month after initial diagnosis of GBM. Conclusions: Primary treatment with inhibitors of BRAF and MEK can lead to tumor regression for patients with BRAFV600E mutant glioblastoma. We therefore recommend that all young GBM patients should undergo BRAFV600E mutation testing, especially for those with unusual aggressive clinical course.-
dc.languageeng-
dc.publisherImpact Journals LLC. The Journal's web site is located at http://www.impactjournals.com/oncotarget/index.html-
dc.relation.ispartofOncotarget-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectBRAF-MEK inhibitors-
dc.subjectBRAFV600E mutation-
dc.subjectglioblastoma-
dc.subjecttargeted therapies-
dc.titleRegression of BRAFV600E mutant adult glioblastoma after primary combined BRAF-MEK inhibitor targeted therapy: a report of two cases-
dc.typeArticle-
dc.identifier.emailLam, TC: lamtc03@hku.hk-
dc.identifier.emailLi, LF: lfrandom@hku.hk-
dc.identifier.emailLeung, RCY: leungrcy@hku.hk-
dc.identifier.authorityLam, TC=rp02128-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.18632/oncotarget.26932-
dc.identifier.pmid31217909-
dc.identifier.pmcidPMC6557198-
dc.identifier.scopuseid_2-s2.0-85066951366-
dc.identifier.hkuros298169-
dc.identifier.volume10-
dc.identifier.issue38-
dc.identifier.spage3818-
dc.identifier.epage3826-
dc.publisher.placeUnited States-

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