Dataset Information

BRAF-mediated brain tumors in adults and children: A review and the Australian and New Zealand experience.

ABSTRACT: The mitogen-activated protein kinase (MAPK) pathway signaling pathway is one of the most commonly mutated pathways in human cancers. In particular, BRAF alterations result in constitutive activation of the rapidly accelerating fibrosarcoma-extracellular signal-regulated kinase-MAPK significant pathway, leading to cellular proliferation, survival, and dedifferentiation. The role of BRAF mutations in oncogenesis and tumorigenesis has spurred the development of targeted agents, which have been successful in treating many adult cancers. Despite advances in other cancer types, the morbidity and survival outcomes of patients with glioma have remained relatively stagnant. Recently, there has been recognition that MAPK dysregulation is almost universally present in paediatric and adult gliomas. These findings, accompanying broad molecular characterization of gliomas, has aided prognostication and offered opportunities for clinical trials testing targeted agents. The use of targeted therapies in this disease represents a paradigm shift, although the biochemical complexities has resulted in unexpected challenges in the development of effective BRAF inhibitors. Despite these challenges, there are promising data to support the use of BRAF inhibitors alone and in combination with MEK inhibitors for patients with both low-grade and high-grade glioma across age groups. Safety and efficacy data demonstrate that many of the toxicities of these targeted agents are tolerable while offering objective responses. Newer clinical trials will examine the use of these therapies in the upfront setting. Appropriate duration of therapy and durability of response remains unclear in the glioma patient cohort. Longitudinal efficacy and toxicity data are needed. Furthermore, access to these medications remains challenging outside of clinical trials in Australia and New Zealand. Compassionate access is limited, and advocacy for mechanism of action-based drug approval is ongoing.

SUBMITTER: Trinder SM

PROVIDER: S-EPMC10140567 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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BRAF-mediated brain tumors in adults and children: A review and the Australian and New Zealand experience.

Trinder Sarah M SM McKay Campbell C Power Phoebe P Topp Monique M Chan Bosco B Valvi Santosh S McCowage Geoffrey G Govender Dinisha D Kirby Maria M Ziegler David S DS Manoharan Neevika N Hassall Tim T Kellie Stewart S Heath John J Alvaro Frank F Wood Paul P Laughton Stephen S Tsui Karen K Dodgshun Andrew A Eisenstat David D DD Endersby Raelene R Luen Stephen J SJ Koh Eng-Siew ES Sim Hao-Wen HW Kong Benjamin B Gottardo Nicholas G NG Whittle James R JR Khuong-Quang Dong-Anh DA Hansford Jordan R JR

Frontiers in oncology 20230414

The mitogen-activated protein kinase (MAPK) pathway signaling pathway is one of the most commonly mutated pathways in human cancers. In particular, BRAF alterations result in constitutive activation of the rapidly accelerating fibrosarcoma-extracellular signal-regulated kinase-MAPK significant pathway, leading to cellular proliferation, survival, and dedifferentiation. The role of BRAF mutations in oncogenesis and tumorigenesis has spurred the development of targeted agents, which have been succ ...[more]

PMID: 37124503

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Dataset Information

BRAF-mediated brain tumors in adults and children: A review and the Australian and New Zealand experience.

Publications

BRAF-mediated brain tumors in adults and children: A review and the Australian and New Zealand experience.

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