TY - JOUR
T1 - Translating current basic research into future therapies for neurofibromatosis type 1
AU - Brosseau, Jean Philippe
AU - Liao, Chung Ping
AU - Le, Lu Q.
N1 - Funding Information:
Funding information L.Q.L. is supported by funding from the National Cancer Institute of the National Institutes of Health (grant number R01 CA166593 and U54 CA196519), the US Department of Defense, the Neurofibromatosis Therapeutic Acceleration Program, the NF1 Research Consortium Fund, and the Giorgio Foundation. J.P.B. and C.P.L. are recipient of the Young Investigator Award from the Children’s Tumor Foundation. J.P.B. is also an Early Investigator Research Award from the US Department of Defense. C.P.L. is also a recipient of the Career Development Award from Dermatology Foundation. L.Q.L. holds a Career Award for Medical Scientists from the Burroughs Wellcome Fund and the Thomas L. Shields, M.D. Professorship in Dermatology.
Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Cancer Research UK.
PY - 2020/7/21
Y1 - 2020/7/21
N2 - Neurofibromatosis type 1 (NF1) is a hereditary tumour syndrome that predisposes to benign and malignant tumours originating from neural crest cells. Biallelic inactivation of the tumour-suppressor gene NF1 in glial cells in the skin, along a nerve plexus or in the brain results in the development of benign tumours: cutaneous neurofibroma, plexiform neurofibroma and glioma, respectively. Despite more than 40 years of research, only one medication was recently approved for treatment of plexiform neurofibroma and no drugs have been specifically approved for the management of other tumours. Work carried out over the past several years indicates that inhibiting different cellular signalling pathways (such as Hippo, Janus kinase/signal transducer and activator of transcription, mitogen-activated protein kinase and those mediated by sex hormones) in tumour cells or targeting cells in the microenvironment (nerve cells, macrophages, mast cells and T cells) might benefit NF1 patients. In this review, we outline previous strategies aimed at targeting these signalling pathways or cells in the microenvironment, agents that are currently in clinical trials, and the latest advances in basic research that could culminate in the development of novel therapeutics for patients with NF1.
AB - Neurofibromatosis type 1 (NF1) is a hereditary tumour syndrome that predisposes to benign and malignant tumours originating from neural crest cells. Biallelic inactivation of the tumour-suppressor gene NF1 in glial cells in the skin, along a nerve plexus or in the brain results in the development of benign tumours: cutaneous neurofibroma, plexiform neurofibroma and glioma, respectively. Despite more than 40 years of research, only one medication was recently approved for treatment of plexiform neurofibroma and no drugs have been specifically approved for the management of other tumours. Work carried out over the past several years indicates that inhibiting different cellular signalling pathways (such as Hippo, Janus kinase/signal transducer and activator of transcription, mitogen-activated protein kinase and those mediated by sex hormones) in tumour cells or targeting cells in the microenvironment (nerve cells, macrophages, mast cells and T cells) might benefit NF1 patients. In this review, we outline previous strategies aimed at targeting these signalling pathways or cells in the microenvironment, agents that are currently in clinical trials, and the latest advances in basic research that could culminate in the development of novel therapeutics for patients with NF1.
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U2 - 10.1038/s41416-020-0903-x
DO - 10.1038/s41416-020-0903-x
M3 - Review article
C2 - 32439933
AN - SCOPUS:85085330617
SN - 0007-0920
VL - 123
SP - 178
EP - 186
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 2
ER -