scholarly journals Complete clinical regression of a BRAF V600E-mutant pediatric glioblastoma multiforme after BRAF inhibitor therapy

BMC Cancer ◽  
2014 ◽  
Vol 14 (1) ◽  
Author(s):  
Giles W Robinson ◽  
Brent A Orr ◽  
Amar Gajjar
Keyword(s):  
Glioblastoma Multiforme ◽  
Braf Inhibitor ◽  
Inhibitor Therapy ◽  
Braf V600e ◽  
Pediatric Glioblastoma

Analysis of plasma-based BRAF and NRAS mutation detection in patients with stage III and IV melanoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9023-9023
Author(s):  
David Polsky ◽  
Jyothirmayee S. Tadepalli ◽  
Shria Hafner ◽  
Gregory Chang ◽  
Nathaniel H. Fleming ◽  
...  
Keyword(s):  
Braf Inhibitor ◽  
Stage Iv ◽  
Inhibitor Therapy ◽  
Braf V600e ◽  
Stage Iii ◽  
Plasma Dna ◽  
Nras Mutation ◽  
Blood Draw ◽  
Tumor Specimen ◽  
Active Disease

9023 Background: Patients with metastatic melanoma are eligible for BRAF inhibitor therapy if the BRAF V600E mutation can be identified in their tumor specimen. Patients lacking an available specimen for genotyping are unable to receive inhibitor therapy. We developed two mutation-specific genotyping platforms and tested their ability to detect BRAF and NRAS mutations in archived plasma and tumor samples to determine the potential utility of blood-based tumor genotyping in melanoma. Methods: We analyzed a group of 96 patients with stage III or IV melanoma, prospectively enrolled and followed in the NYU Melanoma Biorepository program. Each patient had a plasma sample and one or more tumor samples available for analysis. We used a combination of allele-specific PCR (Taqman) and SNaPshot assays to identify BRAF V600 and NRAS Q61 mutations in the tumor and plasma samples. Results: Among the 96 patients, 51 had stage III disease at the time of analysis; 45 had stage IV disease. Seventy-two patients had 2 or more tumor samples available for analysis, for a total of 204 tumors analyzed. In total, 52/96 (54%) patients had one or more BRAF or NRAS mutant tumors, including one patient with separate BRAF and NRAS mutant tumors (BRAF, n=35 (36%); NRAS, n=18 (19%)). We successfully amplified plasma DNA from 39/52 (75%) patients with tumor-associated mutations. Among those patients with amplifiable plasma DNA we detected mutations in 7 (18%) patients including 3 BRAF V600E, one V600K, 2 NRAS Q61K and one Q61L. Plasma-based mutations matched tumor-associated mutations in all 7 patients. All 7 patients had active disease at the time of blood draw. There were 32 patients with tumor-associated mutations in which a mutation could not be detected in the plasma. Only 15 of those 32 (47%) had active disease at the time of blood draw. There were no mutations detected in the plasma of the 44 patients whose tumors lacked BRAF or NRAS mutations. Conclusions: These data suggest that plasma-based detection of BRAF and NRAS mutations has a high specificity for tumor-associated mutations. It may prove to be a useful adjunct to tumor-based genotyping in patients with active disease, especially those lacking an available tumor specimen.

BRAF inhibitor therapy–associated melanocytic lesions lack the BRAF V600E mutation and show increased levels of cyclin D1 expression

2016 ◽  
Vol 50 ◽  
pp. 79-89 ◽  
Author(s):  
Kumaran Mudaliar ◽  
Michael T. Tetzlaff ◽  
Madeleine Duvic ◽  
Ana Ciurea ◽  
Sharon Hymes ◽  
...  
Keyword(s):  
Cyclin D1 ◽  
Braf Inhibitor ◽  
Braf V600e Mutation ◽  
Inhibitor Therapy ◽  
Braf V600e ◽  
Melanocytic Lesions

scholarly journals Efficacy of BRAF‐Inhibitor Therapy in BRAF V600E ‐Mutated Adult Langerhans Cell Histiocytosis

2020 ◽  
Vol 25 (12) ◽  
pp. 1001-1004
Author(s):  
Antonious Z. Hazim ◽  
Gordon J. Ruan ◽  
Aishwarya Ravindran ◽  
Jithma P. Abeykoon ◽  
Caleb Scheckel ◽  
...  
Keyword(s):  
Langerhans Cell Histiocytosis ◽  
Braf Inhibitor ◽  
Langerhans Cell ◽  
Inhibitor Therapy ◽  
Braf V600e

scholarly journals Loss of USP28-mediated BRAF degradation drives resistance to RAF cancer therapies

2018 ◽  
Vol 215 (7) ◽  
pp. 1913-1928 ◽  
Author(s):  
Azad Saei ◽  
Marta Palafox ◽  
Touati Benoukraf ◽  
Nishi Kumari ◽  
Patrick William Jaynes ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Family Members ◽  
Braf Inhibitor ◽  
Inhibitor Therapy ◽  
Braf V600e ◽  
Cancer Therapies ◽  
In Vivo Models ◽  
Mapk Activity ◽  
Key Factor

RAF kinase inhibitors are clinically active in patients with BRAF (V600E) mutant melanoma. However, rarely do tumors regress completely, with the majority of responses being short-lived. This is partially mediated through the loss of negative feedback loops after MAPK inhibition and reactivation of upstream signaling. Here, we demonstrate that the deubiquitinating enzyme USP28 functions through a feedback loop to destabilize RAF family members. Loss of USP28 stabilizes BRAF enhancing downstream MAPK activation and promotes resistance to RAF inhibitor therapy in culture and in vivo models. Importantly, we demonstrate that USP28 is deleted in a proportion of melanoma patients and may act as a biomarker for response to BRAF inhibitor therapy in patients. Furthermore, we identify Rigosertib as a possible therapeutic strategy for USP28-depleted tumors. Our results show that loss of USP28 enhances MAPK activity through the stabilization of RAF family members and is a key factor in BRAF inhibitor resistance.

scholarly journals HGG-02. ADOLESCENT AND YOUNG ADULT (AYA) GLIOMA WITH BRAF V600E-MUTANTATION

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii344-iii344
Author(s):  
Yui Kimura ◽  
Yukitomo Ishi ◽  
Yuko Watanabe ◽  
Yoshiko Nakano ◽  
Shigeru Yamaguchi ◽  
...  
Keyword(s):  
Braf Inhibitor ◽  
Clinical Information ◽  
Early Recurrence ◽  
Pleomorphic Xanthoastrocytoma ◽  
Adolescent And Young Adult ◽  
Braf V600e ◽  
Low Grade ◽  
Diffuse Astrocytoma ◽  
Genetic Features ◽  
Epithelioid Glioblastoma

Abstract BACKGROUND Biological features of pediatric glioma differ significantly from those of adult glioma, and limited data are available on those of AYA patients. Here, we focused on AYA patients with glioma, especially those harboring BRAF V600E mutation, and investigated their clinical and genetic features. METHOD: We retrospectively analyzed AYA patients with brain tumors harboring BRAF V600E, who were treated in two hospitals in Japan. RESULTS Clinical information was available for 14 patients. The median age at diagnosis was 25 years (range: 15–38). Five patients were diagnosed with glioblastoma (GBM), including one epithelioid type. These patients were over 25. Although one patient with GBM died of the disease 6.9 years after initial diagnosis, the remaining patients were alive. Two patients were alive without recurrence at 38 and 51 months after the treatment. The patient with epithelioid glioblastoma experienced early recurrence. The remaining nine patients (64%) were diagnosed with low-grade glioma, including ganglioglioma, pilocytic astrocytoma, diffuse astrocytoma, oligodendroglioma, pleomorphic xanthoastrocytoma, and polymorphous low-grade neuroepithelial tumor of the young. No patients died of the disease, and four patients are alive without recurrence after initial operation without adjuvant treatment. Two patients are (epithelioid glioblastoma and ganglioglioma) currently undergoing treatment with a BRAF inhibitor for recurrent tumors. DISCUSSION Although the number of this study is limited, our study suggested that the prognosis of AYA patients with BRAF-V600E positive GBM may not be as dismal as that of children or adults.

Metastatic Hepatic Angiosarcoma and BRAF Inhibitor Therapy

2017 ◽  
Vol 03 (04) ◽  
Author(s):  
Shweta Gera ◽  
Mark Ettel ◽  
Gabriel Acosta Gonzalez ◽  
Melissa Wilson ◽  
Ruliang Xu
Keyword(s):  
Braf Inhibitor ◽  
Inhibitor Therapy ◽  
Hepatic Angiosarcoma

scholarly journals Durable Response to the Combination of Atezolizumab With Platinum-Based Chemotherapy in an Untreated Non-Smoking Lung Adenocarcinoma Patient With BRAF V600E Mutation: A Case Report

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaomin Niu ◽  
Yingjia Sun ◽  
David Planchard ◽  
Luting Chiu ◽  
Jian Bai ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Nsclc Patient ◽  
Braf Inhibitor ◽  
Progression Free Survival ◽  
Braf V600e ◽  
First Line ◽  
Liquid Biopsies ◽  
Durable Response ◽  
Platinum Based Chemotherapy ◽  
Lung Adenocarcinoma Patient

BackgroundImmune checkpoint inhibitor (ICPi) has become a major treatment in advanced non-small cell lung cancer (NSCLC) and demonstrated a clinical benefit for NSCLC patients with high programmed death ligand-1 (PD-L1) expression without EGFR/ALK/ROS1 drivers; however, the benefit in BRAF V600E NSCLC is so far unknown. Here, we report a case of prolonged tumor response to the combination of immunotherapy with chemotherapy in a non-smoking BRAF V600E NSCLC patient.Materials and MethodsWe verify a co-expression of BRAF V600E mutation and PD-L1 high expression more than 50% on formalin-fixed paraffin-embedded tumor sample of a newly diagnosed lung adenocarcinoma patient by immunohistochemistry and BRAF V600E/EGFR/ALK/ROS1 Mutations Detection Kit. The tissue and liquid biopsies were further subjected to next-generation sequencing (NGS) for identification of mutations with progression on immunotherapy and BRAF inhibitor (BRAFi). The patient had provided written informed consent and authorized the publication of clinical case.ResultsWe demonstrate the case of 62-year-old female non-smoker with high PD-L1 expression and BRAF V600E mutated NSCLC. The progression-free survival (PFS) of first-line combination of atezolizumab with platinum-based chemotherapy and sequential second-line treatment with BRAFi Vemurafenib are 20 and 5.5 months, respectively.ConclusionThis case shows a durable response to ICPi in BRAF V600E non-smoking lung adenocarcinoma with PFS of 20 months under first-line atezolizumab plus chemotherapy treatment. The case supports the idea that the combination immunotherapy may be an attractive option for BRAF V600E mutated non-smoking NSCLC with high PD-L1 expression.

scholarly journals Rapid BRAF mutation detection in melanoma patients by immunohistochemistry

2017 ◽  
Vol 4 (1) ◽  
pp. 1-5
Author(s):  
László Fülöp ◽  
Katalin Götzer ◽  
Erzsébet Csernák ◽  
Danyil Szergejevics Kuznyecov ◽  
Erika Tóth
Keyword(s):  
Braf Inhibitor ◽  
Pcr Amplification ◽  
Diagnostic Algorithm ◽  
Braf V600e ◽  
Wild Type ◽  
Braf Gene ◽  
Braf Mutations ◽  
Activating Mutation ◽  
Melanoma Patients ◽  
Braf V600 Mutation

The V600E mutation is the most common (~90%) activating mutation of the BRAF gene. BRAF mutations have been frequently investigated in melanoma, colorectal cancer and papillary thyroid carcinoma. The importance of the detection of BRAF mutations has been rising by the routine use of Braf inhibitor therapy. We evaluated the usefulness of the BRAF V600E mutation-specific monoclonal antibody (VE1) in metastatic melanoma patients. To confirm the results of immunohistochemistry (IHC), we used COBAS 4800 BRAF V600 mutation test and PCR amplification followed by Sanger sequencing.36 of 105 patients have wild-type BRAF gene, 64 have V600E mutation and 5 of 105 have V600K mutation. Predicting the mutation only by IHC using VE1 antibody, all 58 positively scored specimen were V600E mutant. The V600K, the wild-type patients and 7 patients from the V600E mutant group scored as negative. Thus the specificity is 100% and the positive predictive value is 1 of the IHC method. After processing our data we could establish a cheaper diagnostic algorithm for rapid detection ofBRAF mutation.

scholarly journals Reducing skin toxicities from EGFR inhibitors with topical BRAF inhibitor therapy

2021 ◽  
pp. candisc.1847.2020
Author(s):  
Mario E. Lacouture ◽  
Zev A. Wainberg ◽  
Anisha B Patel ◽  
Milan J Anadkat ◽  
Salomon M Stemmer ◽  
...  
Keyword(s):  
Braf Inhibitor ◽  
Inhibitor Therapy ◽  
Egfr Inhibitors
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