TY - JOUR
T1 - Brain tumors in neurofibromatosis type 1
AU - Costa, Amanda De Andrade
AU - Gutmann, David H.
N1 - Publisher Copyright:
© 2019 The Author(s) 2019. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.
PY - 2020/7/1
Y1 - 2020/7/1
N2 - AbstractAs a cancer predisposition syndrome, individuals with neurofibromatosis type 1 (NF1) are at increased risk for the development of both benign and malignant tumors. One of the most common locations for these cancers is the central nervous system, where low-grade gliomas predominate in children. During early childhood, gliomas affecting the optic pathway are most frequently encountered, whereas gliomas of the brainstem and other locations are observed in slightly older children. In contrast, the majority of gliomas arising in adults with NF1 are malignant cancers, typically glioblastoma, involving the cerebral hemispheres. Our understanding of the pathogenesis of NF1-Associated gliomas has been significantly advanced through the use of genetically engineered mice, yielding new targets for therapeutic drug design and evaluation. In addition, Nf1 murine glioma models have served as instructive platforms for defining the cell of origin of these tumors, elucidating the critical role of the tumor microenvironment in determining tumor growth and vision loss, and determining how cancer risk factors (sex, germline NF1 mutation) impact on glioma formation and progression. Moreover, these preclinical models have permitted early phase analysis of promising drugs that reduce tumor growth and attenuate vision loss, as an initial step prior to translation to human clinical trials.
AB - AbstractAs a cancer predisposition syndrome, individuals with neurofibromatosis type 1 (NF1) are at increased risk for the development of both benign and malignant tumors. One of the most common locations for these cancers is the central nervous system, where low-grade gliomas predominate in children. During early childhood, gliomas affecting the optic pathway are most frequently encountered, whereas gliomas of the brainstem and other locations are observed in slightly older children. In contrast, the majority of gliomas arising in adults with NF1 are malignant cancers, typically glioblastoma, involving the cerebral hemispheres. Our understanding of the pathogenesis of NF1-Associated gliomas has been significantly advanced through the use of genetically engineered mice, yielding new targets for therapeutic drug design and evaluation. In addition, Nf1 murine glioma models have served as instructive platforms for defining the cell of origin of these tumors, elucidating the critical role of the tumor microenvironment in determining tumor growth and vision loss, and determining how cancer risk factors (sex, germline NF1 mutation) impact on glioma formation and progression. Moreover, these preclinical models have permitted early phase analysis of promising drugs that reduce tumor growth and attenuate vision loss, as an initial step prior to translation to human clinical trials.
KW - NF1
KW - RAS
KW - brain tumor
KW - brainstem
KW - glioma
KW - optic pathway
UR - http://www.scopus.com/inward/record.url?scp=85126591897&partnerID=8YFLogxK
U2 - 10.1093/noajnl/vdz040
DO - 10.1093/noajnl/vdz040
M3 - Article
AN - SCOPUS:85126591897
SN - 2632-2498
VL - 2
SP - I85-I97
JO - Neuro-Oncology Advances
JF - Neuro-Oncology Advances
ER -