In healthy cells, the mitogen-activated protein kinase (MAPK) pathway, plays a crucial role in cell signaling, growth and maintenance. However, studies have suggested that the MAPK pathway is a mutation in roughly 58% of tumors. BRAF is one of three RAF kinase subtypes and acts as a signaling node in a major area of the MAPK pathway. Although mostly associated with metastatic melanomas, BRAF mutations have been found in colon cancers, thyroid cancers, and recently gliomas. BRAF activating mutations/fusions are the most common genetic alterations in pediatric low-grade gliomas. Interestingly, hyperactive BRAF signaling has been found to promote oncogene-induced senescence, potentially explaining the more favorable outcome in BRAF-altered brain tumors, and when combined with additional alterations induces tumor growth in human neural stem and progenitor cells. Due to its targetable nature, BRAF could play a significant role in the diagnosis, therapeutic and management of brain tumors.
While targeted therapy for brain tumors is in its infancy, BRAF alterations have been shown, in both pediatric and adult early phase clinical trials, to be effective therapeutic targets using small molecule inhibitors of the MAPK pathway. Low-grade tumors appear to respond durably to these inhibitors, whereas malignant brain tumors often are less responsive and can develop resistance. Much remains to be done to elucidate the best and least toxic therapies for these tumors.
This Research Topic will focus on BRAF-altered brain tumors in both adults and pediatric patients offering a diverse view of the role of the signaling node in subtypes such as high and low-grade pediatric and adult gliomas, pleomorphic xanthoastrocytoma, ganglioglioma, epithelioid glioblastoma, pilocytic astrocytomas, pediatric low-grade glioma, but other more rare malignancies are also welcome. Original research and Review articles should present new data from clinical or basic research as well as analyze or discuss, with innovative and critical observations, previous research. Important topics to discuss include but are not limited to:
1) New approaches to the treatment of BRAF mutated brain tumors.
2) Analysis of brain metastasis with BRAF mutations.
3) New prognostic data on BRAF alterations: beyond the common lesions.
4) The immune system and BRAF-altered brain tumors.
Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.
In healthy cells, the mitogen-activated protein kinase (MAPK) pathway, plays a crucial role in cell signaling, growth and maintenance. However, studies have suggested that the MAPK pathway is a mutation in roughly 58% of tumors. BRAF is one of three RAF kinase subtypes and acts as a signaling node in a major area of the MAPK pathway. Although mostly associated with metastatic melanomas, BRAF mutations have been found in colon cancers, thyroid cancers, and recently gliomas. BRAF activating mutations/fusions are the most common genetic alterations in pediatric low-grade gliomas. Interestingly, hyperactive BRAF signaling has been found to promote oncogene-induced senescence, potentially explaining the more favorable outcome in BRAF-altered brain tumors, and when combined with additional alterations induces tumor growth in human neural stem and progenitor cells. Due to its targetable nature, BRAF could play a significant role in the diagnosis, therapeutic and management of brain tumors.
While targeted therapy for brain tumors is in its infancy, BRAF alterations have been shown, in both pediatric and adult early phase clinical trials, to be effective therapeutic targets using small molecule inhibitors of the MAPK pathway. Low-grade tumors appear to respond durably to these inhibitors, whereas malignant brain tumors often are less responsive and can develop resistance. Much remains to be done to elucidate the best and least toxic therapies for these tumors.
This Research Topic will focus on BRAF-altered brain tumors in both adults and pediatric patients offering a diverse view of the role of the signaling node in subtypes such as high and low-grade pediatric and adult gliomas, pleomorphic xanthoastrocytoma, ganglioglioma, epithelioid glioblastoma, pilocytic astrocytomas, pediatric low-grade glioma, but other more rare malignancies are also welcome. Original research and Review articles should present new data from clinical or basic research as well as analyze or discuss, with innovative and critical observations, previous research. Important topics to discuss include but are not limited to:
1) New approaches to the treatment of BRAF mutated brain tumors.
2) Analysis of brain metastasis with BRAF mutations.
3) New prognostic data on BRAF alterations: beyond the common lesions.
4) The immune system and BRAF-altered brain tumors.
Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.