Advancing RAS/RASopathy therapies: An NCI-sponsored intramural and extramural collaboration for the study of RASopathies.
Biomarkers, Tumor
/ antagonists & inhibitors
Costello Syndrome
/ genetics
Ectodermal Dysplasia
/ genetics
Facies
Failure to Thrive
/ genetics
Heart Defects, Congenital
/ genetics
Humans
Intersectoral Collaboration
Molecular Targeted Therapy
Mutation
National Cancer Institute (U.S.)
Neurofibromatosis 1
/ genetics
Noonan Syndrome
/ genetics
Research Report
Signal Transduction
United States
ras Proteins
/ antagonists & inhibitors
Costello syndrome
Noonan syndrome
RASopathies
Ras/MAP kinase pathway
cardiofaciocutaneous syndrome
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
17
12
2019
accepted:
22
12
2019
pubmed:
9
1
2020
medline:
4
2
2021
entrez:
9
1
2020
Statut:
ppublish
Résumé
RASopathies caused by germline pathogenic variants in genes that encode RAS pathway proteins. These disorders include neurofibromatosis type 1 (NF1), Noonan syndrome (NS), cardiofaciocutaneous syndrome (CFC), and Costello syndrome (CS), and others. RASopathies are characterized by heterogenous manifestations, including congenital heart disease, failure to thrive, and increased risk of cancers. Previous work led by the NCI Pediatric Oncology Branch has altered the natural course of one of the key manifestations of the RASopathy NF1. Through the conduct of a longitudinal cohort study and early phase clinical trials, the MEK inhibitor selumetinib was identified as the first active therapy for the NF1-related peripheral nerve sheath tumors called plexiform neurofibromas (PNs). As a result, selumetinib was granted breakthrough therapy designation by the FDA for the treatment of PN. Other RASopathy manifestations may also benefit from RAS targeted therapies. The overall goal of Advancing RAS/RASopathy Therapies (ART), a new NCI initiative, is to develop effective therapies and prevention strategies for the clinical manifestations of the non-NF1 RASopathies and for tumors characterized by somatic RAS mutations. This report reflects discussions from a February 2019 initiation meeting for this project, which had broad international collaboration from basic and clinical researchers and patient advocates.
Identifiants
pubmed: 31913576
doi: 10.1002/ajmg.a.61485
pmc: PMC7456498
mid: NIHMS1614136
doi:
Substances chimiques
Biomarkers, Tumor
0
ras Proteins
EC 3.6.5.2
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
866-876Subventions
Organisme : NHLBI NIH HHS
ID : R35 HL135742
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA CP010144
Pays : United States
Informations de copyright
Published 2020. This article is a U.S. Government work and is in the public domain in the USA.
Références
J Am Coll Cardiol. 2019 May 7;73(17):2237-2239
pubmed: 31047013
Pediatr Blood Cancer. 2015 Oct;62(10):1709-16
pubmed: 25907661
Cold Spring Harb Perspect Med. 2018 Dec 3;8(12):
pubmed: 29311130
Am J Med Genet A. 2011 Mar;155A(3):486-507
pubmed: 21344638
Nat Genet. 2010 Sep;42(9):794-800
pubmed: 20694012
Cancer Res. 2018 Nov 1;78(21):6297-6307
pubmed: 30115695
Am J Med Genet A. 2004 Jul 1;128A(1):48-51
pubmed: 15211656
Sci Signal. 2013 Apr 02;6(269):pl1
pubmed: 23550210
Clin Genet. 2016 Mar;89(3):359-66
pubmed: 25959749
J Clin Invest. 2011 Mar;121(3):1026-43
pubmed: 21339643
EBioMedicine. 2018 Jan;27:138-150
pubmed: 29254681
Nat Med. 2019 Jul;25(7):1116-1122
pubmed: 31263281
N Engl J Med. 2016 Dec 29;375(26):2550-2560
pubmed: 28029918
Cell Rep. 2015 Oct 20;13(3):504-515
pubmed: 26456833
Nat Genet. 2007 Aug;39(8):1007-12
pubmed: 17603483
Leukemia. 2019 Jan;33(1):181-190
pubmed: 29884903
Science. 2018 Dec 7;362(6419):1177-1182
pubmed: 30442762
Cell. 2018 Jan 25;172(3):578-589.e17
pubmed: 29373830
Curr Opin Genet Dev. 2005 Jun;15(3):265-9
pubmed: 15917201
Circulation. 2019 Jul 16;140(3):207-224
pubmed: 31163979
Brief Funct Genomics. 2012 Jul;11(4):300-10
pubmed: 22753777
Am J Med Genet A. 2016 Aug;170(8):1959-66
pubmed: 27155140
Nat Rev Drug Discov. 2014 Nov;13(11):828-51
pubmed: 25323927
Am J Hum Genet. 2019 Mar 7;104(3):484-491
pubmed: 30803705
Cancer Cell. 2015 Sep 14;28(3):384-98
pubmed: 26343583
Proc Natl Acad Sci U S A. 2019 Feb 12;116(7):2551-2560
pubmed: 30683722
Dis Model Mech. 2015 Sep;8(9):1167
pubmed: 26398161
Cancer Discov. 2018 Feb;8(2):184-195
pubmed: 29247021
Curr Genet Med Rep. 2016 Sep;4(3):57-64
pubmed: 27942422
Hum Mol Genet. 2016 Oct 1;25(R2):R123-R132
pubmed: 27412009
Cancer Res. 2017 Nov 15;77(22):6240-6252
pubmed: 28986383
Am J Med Genet A. 2010 Jan;152A(1):4-24
pubmed: 20014119
Dis Model Mech. 2018 Mar 13;11(3):
pubmed: 29590634
Small GTPases. 2010 Jul;1(1):2-27
pubmed: 21686117
Cancer Biol Ther. 2002 Nov-Dec;1(6):599-606
pubmed: 12642680
PLoS Genet. 2017 Mar 27;13(3):e1006684
pubmed: 28346493
Genes Dev. 2012 Jul 1;26(13):1421-6
pubmed: 22751498
Clin Cancer Res. 2015 Apr 15;21(8):1819-27
pubmed: 25878363
Cancer Discov. 2014 Feb;4(2):216-31
pubmed: 24436047
Mol Cell Biol. 2010 Oct;30(19):4698-711
pubmed: 20679480
J Neurosci. 2016 Jan 6;36(1):142-52
pubmed: 26740656
Am J Med Genet C Semin Med Genet. 2011 May 15;157C(2):83-9
pubmed: 21500339
Commun Integr Biol. 2016 May 18;9(4):e1188241
pubmed: 27574535
Oncogene. 2018 Jun;37(24):3183-3199
pubmed: 29540830
Am J Med Genet A. 2015 Aug;167A(8):1741-6
pubmed: 25900621
Br J Cancer. 2015 Apr 14;112(8):1392-7
pubmed: 25742478
J Clin Invest. 2011 Mar;121(3):1009-25
pubmed: 21339642
Proc Natl Acad Sci U S A. 2016 Jul 5;113(27):7497-502
pubmed: 27313208
Hum Mol Genet. 2006 Feb 15;15(4):543-53
pubmed: 16399795
Proc Natl Acad Sci U S A. 2018 Nov 6;115(45):E10576-E10585
pubmed: 30348783
J Cell Physiol. 2006 Oct;209(1):21-43
pubmed: 16741904
Am J Med Genet C Semin Med Genet. 2016 Dec;172(4):313-331
pubmed: 27862920
Annu Rev Genomics Hum Genet. 2013;14:355-69
pubmed: 23875798
Mol Cell. 2006 Apr 21;22(2):217-30
pubmed: 16630891
Sci Rep. 2017 Nov 8;7(1):14992
pubmed: 29118384
Mol Cell. 2013 Feb 21;49(4):751-8
pubmed: 23352452
Cancer Discov. 2019 Jun;9(6):738-755
pubmed: 30952657
Curr Cancer Drug Targets. 2014;14(6):567-88
pubmed: 25039348
Curr Opin Cell Biol. 2018 Dec;55:42-51
pubmed: 30007125
Nat Cell Biol. 2018 Sep;20(9):1064-1073
pubmed: 30104724
Nature. 2013 Apr 25;496(7446):498-503
pubmed: 23594743
Blood. 2014 Nov 27;124(23):3420-30
pubmed: 25253770
J Biol Chem. 2016 Feb 12;291(7):3124-34
pubmed: 26635368
Proc Natl Acad Sci U S A. 2014 Nov 18;111(46):16395-400
pubmed: 25359213
Clin Cancer Res. 2017 Jun 15;23(12):e83-e90
pubmed: 28620009
Am J Med Genet. 2002 Feb 15;108(1):80-7
pubmed: 11857556
Hum Mol Genet. 2014 Aug 15;23(16):4315-27
pubmed: 24705357
Am J Surg Pathol. 2016 Jul;40(7):876-85
pubmed: 26872011
Dis Model Mech. 2009 Jan-Feb;2(1-2):56-67
pubmed: 19132118
PLoS One. 2017 Jun 5;12(6):e0178905
pubmed: 28582432
Nat Genet. 2019 Sep;51(9):1308-1314
pubmed: 31406347
Am J Med Genet C Semin Med Genet. 2011 May 15;157C(2):136-46
pubmed: 21495172