Targeted MAPK Pathway Inhibitors in Patients With Disseminated Pilocytic Astrocytomas

Drobysheva, Anastasia; Klesse, Laura J.; Bowers, Daniel C.; Rajaram, Veena; Rakheja, Dinesh; Timmons, Charles F.; Wang, Jason; Koral, Korgün; Gargan, Lynn; Ramos, Erica; Park, Jason

doi:10.6004/jnccn.2017.0139

Cited by 25 publications

(17 citation statements)

References 15 publications

(20 reference statements)

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“…10 Trametinib is a MEK inhibitor that is well tolerated in pediatric patients. 11 Given her extreme symptoms and lack of improvement with surgical intervention, our patient was started…”

Section: Discussionmentioning

confidence: 99%

Giant Congenital Melanocytic Nevus Treated With Trametinib

Mir¹,

Agim²,

Kane³

et al. 2019

Pediatrics

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Giant congenital nevi are melanocytic proliferations of the skin that may be complicated by melanoma, neurocutaneous melanocytosis, pain, pruritus, and disfigurement. Current treatment options include surgical resection and medical management of associated symptoms. There is limited efficacy in these modalities. No effective pharmacologic treatments are available for the treatment of these lesions. We present the case of a 7-year-old girl with a giant congenital melanocytic nevus that had an AKAP9-BRAF fusion and was treated with trametinib, which resulted in rapid resolution of the patient's lifelong, intractable pain and pruritus as well as dramatic improvement in the extent of her nevus.

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“…10 Trametinib is a MEK inhibitor that is well tolerated in pediatric patients. 11 Given her extreme symptoms and lack of improvement with surgical intervention, our patient was started…”

Section: Discussionmentioning

confidence: 99%

Giant Congenital Melanocytic Nevus Treated With Trametinib

Mir¹,

Agim²,

Kane³

et al. 2019

Pediatrics

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“…BRAF V600E-mutated PA appears to be associated with an inferior prognosis compared to PA with wild-type BRAF, which may be due to the fact that class I mutations are such strong drivers of ERK signaling and correlate with the relative absence of BRAF fusions in high-grade glioma [72]. A small case series has shown that combined RAF and MEK inhibitor therapy can effect profound responses in patients with BRAF V600E-mutated PA [73].…”

Section: Braf Mutations In Brain Tumor Subtypes and Sensitivity Tomentioning

confidence: 99%

BRAF Mutations and the Utility of RAF and MEK Inhibitors in Primary Brain Tumors

Schreck

Grossman

Pratilas

2019

Cancers

105

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BRAF mutations have been identified as targetable, oncogenic mutations in many cancers. Given the paucity of treatments for primary brain tumors and the poor prognosis associated with high-grade gliomas, BRAF mutations in glioma are of considerable interest. In this review, we present the spectrum of BRAF mutations and fusion alterations present in each class of primary brain tumor based on publicly available databases and publications. We also summarize clinical experience with RAF and MEK inhibitors in patients with primary brain tumors and describe ongoing clinical trials of RAF inhibitors in glioma. Sensitivity to RAF and MEK inhibitors varies among BRAF mutations and between tumor types as only class I BRAF V600 mutations are sensitive to clinically available RAF inhibitors. While class II and III BRAF mutations are found in primary brain tumors, further research is necessary to determine their sensitivity to third-generation RAF inhibitors and/or MEK inhibitors. We recommend that the neuro-oncologist consider using these drugs primarily in the setting of a clinical trial for patients with BRAF-altered glioma in order to advance our knowledge of their efficacy in this patient population.

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“…The BRAF V600E mutation (in addition to other BRAF alterations) is also found more frequently in other glioma subtypes, including pediatric diffuse gliomas and non-infiltrating tumors such as pilocytic astrocytoma and ganglioglioma. Recent studies have shown a response to BRAF inhibitors in some of these cases [162][163][164].…”

Section: Idh-wildtype Glioblastomamentioning

confidence: 99%

Beyond IDH-Mutation: Emerging Molecular Diagnostic and Prognostic Features in Adult Diffuse Gliomas

Mirchia

Richardson

2020

Cancers

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Diffuse gliomas are among the most common adult central nervous system tumors with an annual incidence of more than 16,000 cases in the United States. Until very recently, the diagnosis of these tumors was based solely on morphologic features, however, with the publication of the WHO Classification of Tumours of the Central Nervous System, revised 4th edition in 2016, certain molecular features are now included in the official diagnostic and grading system. One of the most significant of these changes has been the division of adult astrocytomas into IDH-wildtype and IDH-mutant categories in addition to histologic grade as part of the main-line diagnosis, although a great deal of heterogeneity in the clinical outcome still remains to be explained within these categories. Since then, numerous groups have been working to identify additional biomarkers and prognostic factors in diffuse gliomas to help further stratify these tumors in hopes of producing a more complete grading system, as well as understanding the underlying biology that results in differing outcomes. The field of neuro-oncology is currently in the midst of a “molecular revolution” in which increasing emphasis is being placed on genetic and epigenetic features driving current diagnostic, prognostic, and predictive considerations. In this review, we focus on recent advances in adult diffuse glioma biomarkers and prognostic factors and summarize the state of the field.

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Targeted MAPK Pathway Inhibitors in Patients With Disseminated Pilocytic Astrocytomas

Cited by 25 publications

References 15 publications

Giant Congenital Melanocytic Nevus Treated With Trametinib

Giant Congenital Melanocytic Nevus Treated With Trametinib

BRAF Mutations and the Utility of RAF and MEK Inhibitors in Primary Brain Tumors

Beyond IDH-Mutation: Emerging Molecular Diagnostic and Prognostic Features in Adult Diffuse Gliomas

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