Frontiers in Oncology (Apr 2023)
BRAF-mediated brain tumors in adults and children: A review and the Australian and New Zealand experience
- Sarah M. Trinder,
- Campbell McKay,
- Phoebe Power,
- Phoebe Power,
- Monique Topp,
- Bosco Chan,
- Santosh Valvi,
- Geoffrey McCowage,
- Geoffrey McCowage,
- Dinisha Govender,
- Maria Kirby,
- David S. Ziegler,
- David S. Ziegler,
- David S. Ziegler,
- Neevika Manoharan,
- Neevika Manoharan,
- Tim Hassall,
- Stewart Kellie,
- John Heath,
- Frank Alvaro,
- Paul Wood,
- Stephen Laughton,
- Karen Tsui,
- Andrew Dodgshun,
- David D. Eisenstat,
- David D. Eisenstat,
- David D. Eisenstat,
- Raelene Endersby,
- Raelene Endersby,
- Stephen J. Luen,
- Eng-Siew Koh,
- Eng-Siew Koh,
- Eng-Siew Koh,
- Hao-Wen Sim,
- Hao-Wen Sim,
- Hao-Wen Sim,
- Hao-Wen Sim,
- Benjamin Kong,
- Benjamin Kong,
- Nicholas G. Gottardo,
- Nicholas G. Gottardo,
- James R. Whittle,
- Dong-Anh Khuong-Quang,
- Jordan R. Hansford,
- Jordan R. Hansford,
- Jordan R. Hansford
Affiliations
- Sarah M. Trinder
- Department of Paediatric and Adolescent Oncology/Haematology, Perth Children’s Hospital, Nedlands, WA, Australia
- Campbell McKay
- Children’s Cancer Centre, Royal Children’s Hospital, Melbourne, VIC, Australia
- Phoebe Power
- Sydney Children’s Hospital, Children’s Cancer Institute, University of New South Wales, Randwick, NSW, Australia
- Phoebe Power
- School of Women’s and Children’s Health, University of New South Wales, Randwick, NSW, Australia
- Monique Topp
- Department of Medical Oncology, Peter MacCallum Cancer Center, Melbourne, VIC, Australia
- Bosco Chan
- Michael Rice Cancer Centre, Women’s and Children’s Hospital, North Adelaide, SA, Australia
- Santosh Valvi
- Department of Paediatric and Adolescent Oncology/Haematology, Perth Children’s Hospital, Nedlands, WA, Australia
- Geoffrey McCowage
- Department of Oncology, Children’s Hospital at Westmead, Sydney, NSW, Australia
- Geoffrey McCowage
- Australasian Children’s Cancer Trials, Clayton, VIC, Australia
- Dinisha Govender
- Department of Oncology, Children’s Hospital at Westmead, Sydney, NSW, Australia
- Maria Kirby
- Michael Rice Cancer Centre, Women’s and Children’s Hospital, North Adelaide, SA, Australia
- David S. Ziegler
- Sydney Children’s Hospital, Children’s Cancer Institute, University of New South Wales, Randwick, NSW, Australia
- David S. Ziegler
- Children’s Cancer Institute, Lowy Cancer Research Centre, University of New South Wales (UNSW) Sydney, Sydney, NSW, Australia
- David S. Ziegler
- 0School of Clinical Medicine, University of New South Wales (UNSW) Medicine and Health, University of New South Wales (UNSW) Sydney, Sydney, NSW, Australia
- Neevika Manoharan
- Sydney Children’s Hospital, Children’s Cancer Institute, University of New South Wales, Randwick, NSW, Australia
- Neevika Manoharan
- 0School of Clinical Medicine, University of New South Wales (UNSW) Medicine and Health, University of New South Wales (UNSW) Sydney, Sydney, NSW, Australia
- Tim Hassall
- 1Queensland Children’s Hospital, University of Queensland, Brisbane, QLD, Australia
- Stewart Kellie
- 2Westmead Children’s Hospital, University of Sydney, Westmead, NSW, Australia
- John Heath
- 3Department of Pediatric Oncology, Royal Hobart Hospital, Hobart, TAS, Australia
- Frank Alvaro
- 4Department of Pediatric Oncology, John Hunter Children's Hospital, Newcastle, NSW, Australia
- Paul Wood
- 5Monash Medical Centre, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
- Stephen Laughton
- 6Starship Blood and Cancer Centre, Starship Children’s Hospital, Auckland, New Zealand
- Karen Tsui
- 6Starship Blood and Cancer Centre, Starship Children’s Hospital, Auckland, New Zealand
- Andrew Dodgshun
- 7Children’s Haematology/Oncology Centre, Christchurch Hospital, Christchurch, New Zealand
- David D. Eisenstat
- Children’s Cancer Centre, Royal Children’s Hospital, Melbourne, VIC, Australia
- David D. Eisenstat
- 8Murdoch Children’s Research Institute, Melbourne, VIC, Australia
- David D. Eisenstat
- 9Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia
- Raelene Endersby
- 0Brain Tumour Research Program, Telethon Kids Cancer Centre, Telethon Kids Institute, Nedlands, WA, Australia
- Raelene Endersby
- 1Centre for Child Health Research, University of Western Australia, Perth, WA, Australia
- Stephen J. Luen
- 2Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia
- Eng-Siew Koh
- 3Department of Radiation Oncology, Liverpool and Macarther Cancer Therapy Centres, Liverpool, NSW, Australia
- Eng-Siew Koh
- 4Department of Medicine, University of New South Wales, Sydney, NSW, Australia
- Eng-Siew Koh
- 5Ingham Institute for Applied Medical Research, Liverpool, NSW, Australia
- Hao-Wen Sim
- 6National Health and Medical Research Council (NHMRC) Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia
- Hao-Wen Sim
- 7School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia
- Hao-Wen Sim
- 8Department of Medical Oncology, The Kinghorn Cancer Centre, Sydney, NSW, Australia
- Hao-Wen Sim
- 9Department of Medical Oncology, Chris O’Brien Lifehouse, Sydney, NSW, Australia
- Benjamin Kong
- 6National Health and Medical Research Council (NHMRC) Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia
- Benjamin Kong
- 0Department of Medical Oncology, Royal North Shore Hospital, St Leonards, NSW, Australia
- Nicholas G. Gottardo
- Department of Paediatric and Adolescent Oncology/Haematology, Perth Children’s Hospital, Nedlands, WA, Australia
- Nicholas G. Gottardo
- 0Brain Tumour Research Program, Telethon Kids Cancer Centre, Telethon Kids Institute, Nedlands, WA, Australia
- James R. Whittle
- 1Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
- Dong-Anh Khuong-Quang
- Children’s Cancer Centre, Royal Children’s Hospital, Melbourne, VIC, Australia
- Jordan R. Hansford
- Michael Rice Cancer Centre, Women’s and Children’s Hospital, North Adelaide, SA, Australia
- Jordan R. Hansford
- 2South Australian Health and Medical Research Institute South Australia, Adelaide, SA, Australia
- Jordan R. Hansford
- 3South Australia ImmunoGENomics Cancer Institute, University of Adelaide, Adelaide, SA, Australia
- DOI
- https://doi.org/10.3389/fonc.2023.1154246
- Journal volume & issue
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Vol. 13
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.
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