Epigenetic Mechanisms of Escape from BRAF Oncogene Dependency

About eight percent of all human tumors (including 50% of melanomas) carry gain-of-function mutations in the BRAF oncogene. Mutated BRAF and subsequent hyperactivation of the MAPK signaling pathway has motivated the use of MAPK-targeted therapies for these tumors. Despite great promise, however, MAP...

Full description

Saved in:
Bibliographic Details
Published inCancers Vol. 11; no. 10; p. 1480
Main Authors Khaliq, Mehwish, Fallahi-Sichani, Mohammad
Format Journal Article
LanguageEnglish
Published Basel MDPI AG 01.10.2019
MDPI
Subjects
Cancer
Cloning
DNA methylation
Drug resistance
Epigenetics
Gene expression
Gene regulation
Genotype & phenotype
Histones
Kinases
MAP kinase
Melanoma
Mutants
Mutation
Oncogenes
Ovaries
Proteins
Response rates
Review
Signal transduction
Thyroid gland
Tumors
Online AccessGet full text
ISSN2072-6694
2072-6694
DOI10.3390/cancers11101480

Cover

Abstract About eight percent of all human tumors (including 50% of melanomas) carry gain-of-function mutations in the BRAF oncogene. Mutated BRAF and subsequent hyperactivation of the MAPK signaling pathway has motivated the use of MAPK-targeted therapies for these tumors. Despite great promise, however, MAPK-targeted therapies in BRAF-mutant tumors are limited by the emergence of drug resistance. Mechanisms of resistance include genetic, non-genetic and epigenetic alterations. Epigenetic plasticity, often modulated by histone-modifying enzymes and gene regulation, can influence a tumor cell’s BRAF dependency and therefore, response to therapy. In this review, focusing primarily on class 1 BRAF-mutant cells, we will highlight recent work on the contribution of epigenetic mechanisms to inter- and intratumor cell heterogeneity in MAPK-targeted therapy response.
AbstractList About eight percent of all human tumors (including 50% of melanomas) carry gain-of-function mutations in the BRAF oncogene. Mutated BRAF and subsequent hyperactivation of the MAPK signaling pathway has motivated the use of MAPK-targeted therapies for these tumors. Despite great promise, however, MAPK-targeted therapies in BRAF-mutant tumors are limited by the emergence of drug resistance. Mechanisms of resistance include genetic, non-genetic and epigenetic alterations. Epigenetic plasticity, often modulated by histone-modifying enzymes and gene regulation, can influence a tumor cell's BRAF dependency and therefore, response to therapy. In this review, focusing primarily on class 1 BRAF-mutant cells, we will highlight recent work on the contribution of epigenetic mechanisms to inter- and intratumor cell heterogeneity in MAPK-targeted therapy response.About eight percent of all human tumors (including 50% of melanomas) carry gain-of-function mutations in the BRAF oncogene. Mutated BRAF and subsequent hyperactivation of the MAPK signaling pathway has motivated the use of MAPK-targeted therapies for these tumors. Despite great promise, however, MAPK-targeted therapies in BRAF-mutant tumors are limited by the emergence of drug resistance. Mechanisms of resistance include genetic, non-genetic and epigenetic alterations. Epigenetic plasticity, often modulated by histone-modifying enzymes and gene regulation, can influence a tumor cell's BRAF dependency and therefore, response to therapy. In this review, focusing primarily on class 1 BRAF-mutant cells, we will highlight recent work on the contribution of epigenetic mechanisms to inter- and intratumor cell heterogeneity in MAPK-targeted therapy response.
About eight percent of all human tumors (including 50% of melanomas) carry gain-of-function mutations in the BRAF oncogene. Mutated BRAF and subsequent hyperactivation of the MAPK signaling pathway has motivated the use of MAPK-targeted therapies for these tumors. Despite great promise, however, MAPK-targeted therapies in BRAF-mutant tumors are limited by the emergence of drug resistance. Mechanisms of resistance include genetic, non-genetic and epigenetic alterations. Epigenetic plasticity, often modulated by histone-modifying enzymes and gene regulation, can influence a tumor cell’s BRAF dependency and therefore, response to therapy. In this review, focusing primarily on class 1 BRAF-mutant cells, we will highlight recent work on the contribution of epigenetic mechanisms to inter- and intratumor cell heterogeneity in MAPK-targeted therapy response.
Author Fallahi-Sichani, Mohammad
Khaliq, Mehwish
AuthorAffiliation 2 Program in Cancer Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
1 Department of Biomedical Engineering, University of Michigan Medical School, Ann Arbor, MI 48109, USA; mehwishk@umich.edu
3 Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
AuthorAffiliation_xml – name: 2 Program in Cancer Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
– name: 3 Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
– name: 1 Department of Biomedical Engineering, University of Michigan Medical School, Ann Arbor, MI 48109, USA; mehwishk@umich.edu
Author_xml – sequence: 1
  givenname: Mehwish
  surname: Khaliq
  fullname: Khaliq, Mehwish
– sequence: 2
  givenname: Mohammad
  orcidid: 0000-0003-0917-3525
  surname: Fallahi-Sichani
  fullname: Fallahi-Sichani, Mohammad
BookMark eNqFUE1PGzEQtSoQUMqZ60pcuKTY66_dA0iQJi1SEFIFZ8vrjMHRrr3Yu6D8-zoKUmkOxYfxSPPem3nvK9rzwQNCpwR_p7TGF0Z7AzERQjBhFf6Cjkosy4kQNdv70B-ik5RWOD9KiRTyAB1SwivCuTxCl7PePYGHwZniDsyz9i51qQi2mCWjeyhsDF1x8_t6Xtx7EzbQ4gf04Jfgzfob2re6TXDy_h-jx_nsYfprsrj_eTu9XkwME2yY1A3XmFtNuSWVIZBbVst6WePGNrk0tjYGOKuNIBKw0FJSmy0tCSkx00CPEd7qjr7X6zfdtqqPrtNxrQhWmzDUThiZcrWl9GPTwdKAH6L-SwvaqX8n3j2rp_CqRFUKIaoscP4uEMPLCGlQnUsG2lZ7CGNSJc2LGBe8zNCzHegqjNHnRFTJmeRcYL65iG9RJoaUIlhl3KAHFzb7XfsfJxc7vM-8_wHZD6VK
CitedBy_id crossref_primary_10_3390_cells10082048
crossref_primary_10_1016_j_semcancer_2021_03_013
crossref_primary_10_1007_s10147_023_02318_w
crossref_primary_10_1016_j_neo_2020_06_006
crossref_primary_10_3390_cancers15164026
crossref_primary_10_1016_j_toxrep_2022_03_037
crossref_primary_10_3390_ijms21031102
crossref_primary_10_3390_ijms241914837
crossref_primary_10_1016_j_tem_2023_11_005
crossref_primary_10_1016_j_critrevonc_2021_103234
crossref_primary_10_1038_s41571_023_00852_0
crossref_primary_10_1158_1541_7786_MCR_21_0038
crossref_primary_10_3390_ijms23179985
crossref_primary_10_3390_jpm11090901
crossref_primary_10_3390_ijms21134576
crossref_primary_10_1371_journal_pcbi_1007688
crossref_primary_10_1080_17425247_2021_1825377
crossref_primary_10_3389_freae_2024_1423454
crossref_primary_10_1371_journal_pone_0249388
crossref_primary_10_1038_s12276_022_00836_7
crossref_primary_10_3390_life11050424
crossref_primary_10_1016_j_celrep_2022_111601
crossref_primary_10_1093_ejendo_lvac011
crossref_primary_10_3390_cancers14061532
Cites_doi 10.1016/j.cell.2018.04.012
10.1016/j.bcp.2016.06.014
10.1073/pnas.0506580102
10.1038/ng.907
10.18632/oncotarget.23654
10.1158/2159-8290.CD-13-0642
10.1016/j.celrep.2013.08.023
10.1038/onc.2010.408
10.1016/j.trecan.2019.02.003
10.1126/science.1170116
10.1016/j.ccell.2018.10.014
10.1677/erc.0.0080219
10.1038/nature22794
10.1038/nrc.2017.79
10.1016/j.celrep.2016.02.010
10.1038/nrclinonc.2017.166
10.1126/science.1169786
10.1038/nrc3130
10.1016/j.ygeno.2015.09.004
10.1016/0888-7543(92)90024-M
10.1111/j.1755-148X.2010.00685.x
10.1038/nrg3554
10.1038/nrm3979
10.1016/j.celrep.2017.03.078
10.1158/2159-8290.CD-13-0631
10.1093/jnci/95.6.484
10.1038/nm.3392
10.1038/nature09627
10.1158/1078-0432.CCR-09-2006
10.1016/S0140-6736(12)60868-X
10.1126/science.1210597
10.1073/pnas.1004900107
10.1038/35065000
10.1056/NEJMoa1406037
10.1126/science.aaw3472
10.1053/jhep.2001.22507
10.1073/pnas.0905833106
10.1038/s41591-018-0274-5
10.1016/S1470-2045(18)30142-6
10.1016/j.ccell.2015.03.008
10.1093/nar/gkq929
10.15252/msb.20145877
10.1038/ng.298
10.1038/onc.2014.372
10.1056/NEJMoa1112302
10.1056/NEJMoa1412690
10.1038/ncomms6694
10.1038/emboj.2012.100
10.1158/2159-8290.CD-12-0386
10.1126/science.aad0501
10.1016/j.ccell.2016.06.024
10.1158/2159-8290.CD-18-1321
10.1158/1078-0432.CCR-13-0657
10.1038/nature23297
10.1056/NEJMoa1502309
10.1038/ncomms7051
10.1016/j.cell.2018.02.037
10.1038/nature03672
10.1200/JCO.2005.01.5180
10.1056/NEJMoa1210093
10.1056/NEJMoa1103782
10.1038/s41388-019-0729-2
10.1136/gut.2003.037671
10.1371/journal.pone.0015588
10.1056/NEJMoa1105358
10.1038/nature13121
10.1038/nature23007
10.1200/JCO.2010.33.1280
10.1073/pnas.1525619113
10.1038/nature14982
10.1371/journal.pone.0085004
10.1016/S0140-6736(15)60898-4
10.1126/science.aal2380
10.1038/nm.4040
10.1158/0008-5472.CAN-11-2023
10.1016/j.cell.2013.03.008
10.1186/s12885-015-1811-y
10.1158/1078-0432.CCR-10-2200
10.15252/emmm.201607156
10.1038/ng.3218
10.1038/nrd4281
10.1158/0008-5472.CAN-10-2954
10.1158/0008-5472.CAN-05-1683
10.1038/s41591-018-0158-8
10.1038/nature10662
10.1016/j.ccr.2012.10.009
10.1038/nature09626
10.1158/2159-8290.CD-15-0896
10.1038/ncomms10690
10.1126/science.1210944
10.1038/nature08833
10.1016/j.cell.2018.02.060
10.1016/j.cell.2010.04.020
10.1038/nature08514
10.1093/jnci/dju106
10.1016/j.molcel.2012.12.018
10.1111/j.1349-7006.2010.01712.x
10.1038/nature08902
10.1101/gad.219626.113
10.1016/j.ccr.2014.03.011
10.1038/nature00766
10.1038/ng.3228
10.1038/nature11538
10.15252/emmm.201708446
10.1038/nature09454
10.1016/j.ccr.2010.11.023
10.1038/nature24297
10.1016/j.cell.2015.07.061
10.1002/pmic.201400200
10.1016/j.cell.2013.09.034
10.1038/nature23291
10.1038/nm0795-686
10.1016/j.ccell.2018.01.013
10.1038/labinvest.2017.9
10.15252/msb.20166796
10.1074/jbc.274.12.7936
10.1016/j.cell.2009.12.040
10.1038/nature13385
10.1172/JCI72763
10.1158/2159-8290.CD-18-0879
10.1158/0008-5472.CAN-10-0902
10.1002/cam4.667
10.1016/j.cell.2018.06.025
10.1016/j.cell.2010.02.027
10.1038/sj.onc.1210421
10.1016/j.ccell.2015.08.001
10.1158/2159-8290.CD-14-1518
10.1038/s41571-019-0204-6
10.1038/ng1834
10.1158/2159-8290.CD-13-0279
10.1038/onc.2017.341
10.1038/ncomms6712
10.1038/modpathol.2017.104
10.1016/j.ccell.2016.02.003
10.1073/pnas.0711741105
10.1038/nature05660
10.1200/JCO.2018.78.9990
10.1038/nm.4091
10.1016/S0092-8674(04)00215-6
10.1038/nature09806
10.1016/j.celrep.2013.03.025
10.1126/science.1063127
10.1016/j.ccell.2018.01.002
10.1016/j.ccr.2013.05.003
10.1200/JCO.2010.33.2312
10.1073/pnas.1320956111
10.1038/ng.2291
10.1158/2159-8290.CD-12-0470
10.1038/s41467-018-05966-z
10.1038/nature12688
10.1016/j.ccell.2018.03.017
10.1038/ncponc0558
10.1016/j.ccell.2014.11.018
10.1073/pnas.1712064115
10.1158/2159-8290.CD-17-1227
10.1101/gad.2037511
10.1038/s41568-019-0154-4
10.1158/2159-8290.CD-13-0424
10.1158/2159-8290.CD-13-0617
10.1038/nature14336
ContentType Journal Article
Copyright 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
2019 by the authors. 2019
Copyright_xml – notice: 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
– notice: 2019 by the authors. 2019
DBID AAYXX
CITATION
3V.
7T5
7TO
7XB
8FE
8FH
8FK
8G5
ABUWG
AFKRA
AZQEC
BBNVY
BENPR
BHPHI
CCPQU
DWQXO
GNUQQ
GUQSH
H94
HCIFZ
LK8
M2O
M7P
MBDVC
PHGZM
PHGZT
PIMPY
PKEHL
PQEST
PQGLB
PQQKQ
PQUKI
PRINS
Q9U
7X8
5PM
ADTOC
UNPAY
DOI 10.3390/cancers11101480
DatabaseName CrossRef
ProQuest Central (Corporate)
Immunology Abstracts
Oncogenes and Growth Factors Abstracts
ProQuest Central (purchase pre-March 2016)
ProQuest SciTech Collection
ProQuest Natural Science Collection
ProQuest Central (Alumni) (purchase pre-March 2016)
Research Library (Alumni)
ProQuest Central (Alumni)
ProQuest Central UK/Ireland
ProQuest Central Essentials
Biological Science Collection
ProQuest Central
Natural Science Collection
ProQuest One Community College
ProQuest Central Korea
ProQuest Central Student
ProQuest Research Library
AIDS and Cancer Research Abstracts
SciTech Premium Collection (via ProQuest)
Biological Sciences
Research Library
Biological Science Database
Research Library (Corporate)
Proquest Central Premium
ProQuest One Academic (New)
Publicly Available Content Database
ProQuest One Academic Middle East (New)
ProQuest One Academic Eastern Edition (DO NOT USE)
ProQuest One Applied & Life Sciences
ProQuest One Academic
ProQuest One Academic UKI Edition
ProQuest Central China
ProQuest Central Basic
MEDLINE - Academic
PubMed Central (Full Participant titles)
Unpaywall for CDI: Periodical Content
Unpaywall
DatabaseTitle CrossRef
Publicly Available Content Database
Research Library Prep
ProQuest Central Student
Oncogenes and Growth Factors Abstracts
ProQuest One Academic Middle East (New)
ProQuest Central Essentials
ProQuest Central (Alumni Edition)
SciTech Premium Collection
ProQuest One Community College
Research Library (Alumni Edition)
ProQuest Natural Science Collection
ProQuest Central China
ProQuest Central
ProQuest One Applied & Life Sciences
Natural Science Collection
ProQuest Central Korea
Biological Science Collection
AIDS and Cancer Research Abstracts
ProQuest Research Library
ProQuest Central (New)
ProQuest Biological Science Collection
ProQuest Central Basic
ProQuest One Academic Eastern Edition
Biological Science Database
ProQuest SciTech Collection
ProQuest One Academic UKI Edition
Immunology Abstracts
ProQuest One Academic
ProQuest One Academic (New)
ProQuest Central (Alumni)
MEDLINE - Academic
DatabaseTitleList MEDLINE - Academic
CrossRef
Publicly Available Content Database
Database_xml – sequence: 1
  dbid: UNPAY
  name: Unpaywall
  url: https://proxy.k.utb.cz/login?url=https://unpaywall.org/
  sourceTypes: Open Access Repository
– sequence: 2
  dbid: BENPR
  name: ProQuest Central
  url: http://www.proquest.com/pqcentral?accountid=15518
  sourceTypes: Aggregation Database
DeliveryMethod fulltext_linktorsrc
Discipline Medicine
EISSN 2072-6694
ExternalDocumentID 10.3390/cancers11101480
PMC6826668
10_3390_cancers11101480
GroupedDBID ---
53G
5VS
8FE
8FH
8G5
AADQD
AAFWJ
AAYXX
ABDBF
ABUWG
ACUHS
ADBBV
AFKRA
AFZYC
ALMA_UNASSIGNED_HOLDINGS
AOIJS
AZQEC
BAWUL
BBNVY
BCNDV
BENPR
BHPHI
BPHCQ
CCPQU
CITATION
DIK
DWQXO
E3Z
EBD
ESX
GNUQQ
GUQSH
GX1
HCIFZ
HYE
IAO
IHR
KQ8
LK8
M2O
M48
M7P
MODMG
M~E
OK1
P6G
PGMZT
PHGZM
PHGZT
PIMPY
PQGLB
PQQKQ
PROAC
PUEGO
RPM
TUS
3V.
7T5
7TO
7XB
8FK
H94
MBDVC
PKEHL
PQEST
PQUKI
PRINS
Q9U
7X8
5PM
ADRAZ
ADTOC
C1A
IPNFZ
ITC
RIG
UNPAY
ID FETCH-LOGICAL-c464t-9b5a05fa35f18c1e5fa4979d90bfb90bbf9cce549c617e06a773f148d11204ae3
IEDL.DBID UNPAY
ISSN 2072-6694
IngestDate Tue Aug 19 23:21:49 EDT 2025
Tue Sep 30 16:36:22 EDT 2025
Fri Sep 05 11:20:48 EDT 2025
Fri Jul 25 12:12:23 EDT 2025
Wed Oct 01 02:34:49 EDT 2025
Thu Apr 24 22:56:10 EDT 2025
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 10
Language English
License https://creativecommons.org/licenses/by/4.0
Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
cc-by
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c464t-9b5a05fa35f18c1e5fa4979d90bfb90bbf9cce549c617e06a773f148d11204ae3
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
ObjectType-Review-3
content type line 23
ORCID 0000-0003-0917-3525
OpenAccessLink https://proxy.k.utb.cz/login?url=https://www.mdpi.com/2072-6694/11/10/1480/pdf?version=1570025965
PMID 31581557
PQID 2547556050
PQPubID 2032421
ParticipantIDs unpaywall_primary_10_3390_cancers11101480
pubmedcentral_primary_oai_pubmedcentral_nih_gov_6826668
proquest_miscellaneous_2301445652
proquest_journals_2547556050
crossref_citationtrail_10_3390_cancers11101480
crossref_primary_10_3390_cancers11101480
ProviderPackageCode CITATION
AAYXX
PublicationCentury 2000
PublicationDate 2019-10-01
PublicationDateYYYYMMDD 2019-10-01
PublicationDate_xml – month: 10
  year: 2019
  text: 2019-10-01
  day: 01
PublicationDecade 2010
PublicationPlace Basel
PublicationPlace_xml – name: Basel
PublicationTitle Cancers
PublicationYear 2019
Publisher MDPI AG
MDPI
Publisher_xml – name: MDPI AG
– name: MDPI
References Emery (ref_104) 2009; 106
Robert (ref_8) 2015; 372
Lin (ref_161) 2015; 47
Saito (ref_148) 2001; 33
Strub (ref_116) 2018; 9
Chen (ref_82) 2016; 6
Lavoie (ref_61) 2015; 16
Guterres (ref_164) 2018; 10
ref_10
Su (ref_90) 2012; 366
Kaneda (ref_141) 2011; 102
Bai (ref_126) 2019; 16
Lin (ref_30) 2014; 111
Krijgsman (ref_44) 2014; 5
Paoluzzi (ref_163) 2016; 5
Baylin (ref_138) 2011; 11
Wagle (ref_12) 2014; 4
Yu (ref_48) 2018; 33
Tsoi (ref_5) 2018; 33
Karoulia (ref_75) 2017; 17
Xu (ref_66) 2003; 63
Subramanian (ref_33) 2005; 102
Hata (ref_51) 2016; 22
Gopal (ref_40) 2010; 70
Freeman (ref_70) 2013; 49
Fang (ref_146) 2016; 113
Sack (ref_114) 2018; 173
Wagle (ref_20) 2014; 4
Whittaker (ref_105) 2013; 3
Emmons (ref_25) 2016; 122
Moriceau (ref_21) 2015; 27
Fiziev (ref_50) 2017; 19
Yao (ref_97) 2019; 25
Perotti (ref_169) 2019; 38
Smith (ref_24) 2016; 29
Singer (ref_59) 2003; 95
Tirosh (ref_46) 2016; 352
Rambow (ref_26) 2018; 174
Heidorn (ref_73) 2010; 140
Roesch (ref_28) 2010; 141
Wagner (ref_158) 2018; 33
Long (ref_101) 2015; 386
Roesch (ref_29) 2013; 23
Moerke (ref_38) 2015; 11
Davies (ref_57) 2002; 417
Paraiso (ref_106) 2011; 71
Kambara (ref_144) 2004; 53
Shaffer (ref_47) 2017; 546
Kriaucionis (ref_129) 2009; 324
Lito (ref_37) 2012; 22
Emmanuel (ref_160) 2015; 47
ref_74
Wan (ref_71) 2004; 116
Nazarian (ref_16) 2010; 468
Lister (ref_136) 2009; 462
Gilmartin (ref_99) 2011; 17
Konieczkowski (ref_45) 2014; 4
Brennan (ref_67) 2013; 155
Hauschild (ref_11) 2012; 380
Kane (ref_140) 1997; 57
Perego (ref_27) 2018; 37
Cardarella (ref_62) 2013; 19
Kawakami (ref_122) 2017; 97
Chatterjee (ref_119) 2019; 5
Johannessen (ref_43) 2013; 504
Poulikakos (ref_93) 2010; 464
Herr (ref_69) 2012; 31
Das (ref_31) 2015; 34
Shen (ref_154) 2013; 153
Ikawa (ref_81) 1988; 8
ref_84
Wang (ref_127) 2018; 173
Cheng (ref_64) 2018; 31
Ahronian (ref_103) 2015; 5
Fujimoto (ref_155) 2012; 44
Dummer (ref_87) 2018; 19
Hangauer (ref_118) 2017; 551
Yao (ref_72) 2017; 548
Haigis (ref_113) 2019; 363
Sharma (ref_32) 2010; 141
Smith (ref_121) 2017; 9
He (ref_131) 2011; 333
Sosman (ref_3) 2012; 366
Villanueva (ref_19) 2013; 4
Long (ref_100) 2014; 371
Gui (ref_156) 2011; 43
Maertens (ref_166) 2019; 9
Lito (ref_111) 2013; 19
Ito (ref_128) 2011; 333
Girault (ref_147) 2003; 9
Weisenberger (ref_143) 2006; 38
Jenuwein (ref_151) 2001; 293
Jin (ref_137) 2011; 71
ref_56
Halaban (ref_91) 2010; 23
Ceol (ref_157) 2011; 471
Bachmann (ref_167) 2006; 24
Tsai (ref_85) 2008; 105
Gonsalves (ref_65) 2014; 106
Larsen (ref_132) 1992; 13
Seligson (ref_153) 2005; 435
Wagle (ref_18) 2011; 29
Ramirez (ref_52) 2016; 7
Voigt (ref_152) 2013; 27
Sun (ref_36) 2014; 508
Viswanathan (ref_115) 2017; 547
Bivona (ref_6) 2016; 22
Marzese (ref_150) 2018; 9
Arozarena (ref_120) 2019; 19
ref_60
Becker (ref_35) 2017; 13
Hinohara (ref_117) 2018; 34
Shaw (ref_112) 2018; 15
Plass (ref_135) 2013; 14
Paik (ref_63) 2011; 29
Kleyman (ref_9) 2018; 8
Long (ref_22) 2014; 5
Zhang (ref_96) 2015; 526
Yao (ref_95) 2015; 28
Weinstein (ref_2) 2006; 3
Zingg (ref_168) 2015; 6
Lito (ref_98) 2014; 25
Karoulia (ref_94) 2016; 30
Hyman (ref_4) 2015; 373
Taube (ref_159) 2010; 107
Irizarry (ref_134) 2009; 41
Lyons (ref_83) 2001; 8
Villanueva (ref_107) 2010; 18
Johannessen (ref_109) 2010; 468
Yagi (ref_142) 2010; 16
Nieto (ref_76) 2017; 548
Bailey (ref_1) 2018; 173
Forbes (ref_79) 2011; 39
Imielinski (ref_77) 2014; 124
Emuss (ref_78) 2005; 65
Shi (ref_14) 2014; 4
Poulikakos (ref_17) 2011; 480
Tahiliani (ref_130) 2009; 324
Shi (ref_23) 2014; 4
Deaton (ref_133) 2011; 25
Merlo (ref_139) 1995; 1
Mica (ref_125) 2013; 3
Zanconato (ref_162) 2018; 24
Landsberg (ref_124) 2012; 490
Hirata (ref_42) 2015; 27
Yaeger (ref_88) 2019; 9
Flaherty (ref_13) 2012; 367
Micevic (ref_149) 2016; 14
Chang (ref_53) 2001; 410
Samatar (ref_110) 2014; 13
Flavahan (ref_49) 2017; 357
Kaley (ref_68) 2018; 36
Chapman (ref_7) 2011; 364
Bollag (ref_86) 2010; 467
Stanton (ref_80) 1987; 7
Fedorenko (ref_39) 2015; 15
Kimura (ref_58) 2003; 63
Kaplan (ref_89) 2011; 30
ref_102
Obenauf (ref_41) 2015; 520
Lee (ref_165) 1999; 274
Hatzivassiliou (ref_92) 2010; 464
Lin (ref_123) 2007; 445
Dhillon (ref_54) 2007; 26
Weber (ref_55) 2001; 61
Girotti (ref_108) 2013; 3
Su (ref_34) 2017; 114
Jin (ref_145) 2015; 106
Hugo (ref_15) 2015; 162
References_xml – volume: 63
  start-page: 4561
  year: 2003
  ident: ref_66
  article-title: High Prevalence of BRAF Gene Mutation in Papillary Thyroid Carcinomas and Thyroid Tumor Cell Lines
  publication-title: Cancer Res.
– volume: 173
  start-page: 1413
  year: 2018
  ident: ref_127
  article-title: An Acquired Vulnerability of Drug-Resistant Melanoma with Therapeutic Potential
  publication-title: Cell
  doi: 10.1016/j.cell.2018.04.012
– volume: 122
  start-page: 1
  year: 2016
  ident: ref_25
  article-title: The Role of Phenotypic Plasticity in the Escape of Cancer Cells from Targeted Therapy
  publication-title: Biochem. Pharmacol.
  doi: 10.1016/j.bcp.2016.06.014
– volume: 102
  start-page: 15545
  year: 2005
  ident: ref_33
  article-title: Gene Set Enrichment Analysis: A Knowledge-Based Approach for Interpreting Genome-Wide Expression Profiles
  publication-title: Proc. Natl. Acad. Sci. USA
  doi: 10.1073/pnas.0506580102
– volume: 43
  start-page: 875
  year: 2011
  ident: ref_156
  article-title: Frequent Mutations of Chromatin Remodeling Genes in Transitional Cell Carcinoma of the Bladder
  publication-title: Nat. Genet.
  doi: 10.1038/ng.907
– volume: 9
  start-page: 8206
  year: 2018
  ident: ref_150
  article-title: Distinct Histone Modifications Denote Early Stress-Induced Drug Tolerance in Cancer
  publication-title: Oncotarget
  doi: 10.18632/oncotarget.23654
– volume: 4
  start-page: 80
  year: 2014
  ident: ref_14
  article-title: Acquired Resistance and Clonal Evolution in Melanoma during BRAF Inhibitor Therapy
  publication-title: Cancer Discov.
  doi: 10.1158/2159-8290.CD-13-0642
– volume: 4
  start-page: 1090
  year: 2013
  ident: ref_19
  article-title: Concurrent MEK2 Mutation and BRAF Amplification Confer Resistance to BRAF and MEK Inhibitors in Melanoma
  publication-title: Cell Rep.
  doi: 10.1016/j.celrep.2013.08.023
– volume: 30
  start-page: 366
  year: 2011
  ident: ref_89
  article-title: Hyperactivation of MEK-ERK1/2 Signaling and Resistance to Apoptosis Induced by the Oncogenic B-RAF Inhibitor, PLX4720, in Mutant N-RAS Melanoma Cells
  publication-title: Oncogene
  doi: 10.1038/onc.2010.408
– volume: 5
  start-page: 170
  year: 2019
  ident: ref_119
  article-title: Polytherapy and Targeted Cancer Drug Resistance
  publication-title: Trends Cancer
  doi: 10.1016/j.trecan.2019.02.003
– volume: 324
  start-page: 930
  year: 2009
  ident: ref_130
  article-title: Conversion of 5-Methylcytosine to 5-Hydroxymethylcytosine in Mammalian DNA by MLL Partner TET1
  publication-title: Science
  doi: 10.1126/science.1170116
– volume: 34
  start-page: 939
  year: 2018
  ident: ref_117
  article-title: KDM5 Histone Demethylase Activity Links Cellular Transcriptomic Heterogeneity to Therapeutic Resistance
  publication-title: Cancer Cell
  doi: 10.1016/j.ccell.2018.10.014
– volume: 8
  start-page: 219
  year: 2001
  ident: ref_83
  article-title: Discovery of a Novel Raf Kinase Inhibitor
  publication-title: Endocr. Relat. Cancer
  doi: 10.1677/erc.0.0080219
– volume: 546
  start-page: 431
  year: 2017
  ident: ref_47
  article-title: Rare Cell Variability and Drug-Induced Reprogramming As a Mode of Cancer Drug Resistance
  publication-title: Nature
  doi: 10.1038/nature22794
– volume: 17
  start-page: 676
  year: 2017
  ident: ref_75
  article-title: New Perspectives for Targeting RAF Kinase in Human Cancer
  publication-title: Nat. Rev. Cancer
  doi: 10.1038/nrc.2017.79
– volume: 14
  start-page: 2180
  year: 2016
  ident: ref_149
  article-title: DNMT3b Modulates Melanoma Growth by Controlling Levels of mTORC2 Component RICTOR
  publication-title: Cell Rep.
  doi: 10.1016/j.celrep.2016.02.010
– volume: 15
  start-page: 81
  year: 2018
  ident: ref_112
  article-title: Tumour Heterogeneity and Resistance to Cancer Therapies
  publication-title: Nat. Rev. Clin. Oncol.
  doi: 10.1038/nrclinonc.2017.166
– volume: 324
  start-page: 929
  year: 2009
  ident: ref_129
  article-title: The Nuclear DNA Base 5-Hydroxymethylcytosine is Present in Purkinje Neurons and the Brain
  publication-title: Science
  doi: 10.1126/science.1169786
– volume: 11
  start-page: 726
  year: 2011
  ident: ref_138
  article-title: A Decade of Exploring the Cancer Epigenome—Biological and Translational Implications
  publication-title: Nat. Rev. Cancer
  doi: 10.1038/nrc3130
– volume: 106
  start-page: 322
  year: 2015
  ident: ref_145
  article-title: The DNA Methylation Landscape of Human Melanoma
  publication-title: Genomics
  doi: 10.1016/j.ygeno.2015.09.004
– volume: 13
  start-page: 1095
  year: 1992
  ident: ref_132
  article-title: CpG Islands As Gene Markers in the Human Genome
  publication-title: Genomics
  doi: 10.1016/0888-7543(92)90024-M
– volume: 57
  start-page: 808
  year: 1997
  ident: ref_140
  article-title: Methylation of the hMLH1 Promoter Correlates with Lack of Expression of hMLH1 in Sporadic Colon Tumors and Mismatch Repair-Defective Human Tumor Cell Lines
  publication-title: Cancer Res.
– volume: 23
  start-page: 190
  year: 2010
  ident: ref_91
  article-title: PLX4032, a Selective BRAF(V600E) Kinase Inhibitor, Activates the ERK Pathway and Enhances Cell Migration and Proliferation of BRAF Melanoma Cells
  publication-title: Pigment Cell Melanoma Res.
  doi: 10.1111/j.1755-148X.2010.00685.x
– volume: 14
  start-page: 765
  year: 2013
  ident: ref_135
  article-title: Mutations in Regulators of the Epigenome and Their Connections to Global Chromatin Patterns in Cancer
  publication-title: Nat. Rev. Genet.
  doi: 10.1038/nrg3554
– volume: 16
  start-page: 281
  year: 2015
  ident: ref_61
  article-title: Regulation of RAF Protein Kinases in ERK Signalling
  publication-title: Nat. Rev. Mol. Cell Biol.
  doi: 10.1038/nrm3979
– volume: 19
  start-page: 875
  year: 2017
  ident: ref_50
  article-title: Systematic Epigenomic Analysis Reveals Chromatin States Associated with Melanoma Progression
  publication-title: Cell Rep.
  doi: 10.1016/j.celrep.2017.03.078
– ident: ref_56
– volume: 4
  start-page: 61
  year: 2014
  ident: ref_12
  article-title: MAP Kinase Pathway Alterations in BRAF-Mutant Melanoma Patients with Acquired Resistance to Combined RAF/MEK Inhibition
  publication-title: Cancer Discov.
  doi: 10.1158/2159-8290.CD-13-0631
– volume: 95
  start-page: 484
  year: 2003
  ident: ref_59
  article-title: Mutations in BRAF and KRAS Characterize the Development of Low-Grade Ovarian Serous Carcinoma
  publication-title: J. Natl. Cancer Inst.
  doi: 10.1093/jnci/95.6.484
– volume: 7
  start-page: 1171
  year: 1987
  ident: ref_80
  article-title: Activation of Human Raf Transforming Genes by Deletion of Normal Amino-Terminal Coding Sequences
  publication-title: Mol. Cell. Biol.
– volume: 19
  start-page: 1401
  year: 2013
  ident: ref_111
  article-title: Tumor Adaptation and Resistance to RAF Inhibitors
  publication-title: Nat. Med.
  doi: 10.1038/nm.3392
– volume: 9
  start-page: 4415
  year: 2003
  ident: ref_147
  article-title: Expression Analysis of DNA Methyltransferases 1, 3A, and 3B in Sporadic Breast Carcinomas
  publication-title: Clin. Cancer Res.
– ident: ref_10
– volume: 468
  start-page: 968
  year: 2010
  ident: ref_109
  article-title: COT Drives Resistance to RAF Inhibition Through MAP Kinase Pathway Reactivation
  publication-title: Nature
  doi: 10.1038/nature09627
– volume: 16
  start-page: 21
  year: 2010
  ident: ref_142
  article-title: Three DNA Methylation Epigenotypes in Human Colorectal Cancer
  publication-title: Clin. Cancer Res.
  doi: 10.1158/1078-0432.CCR-09-2006
– volume: 61
  start-page: 3595
  year: 2001
  ident: ref_55
  article-title: Active Ras Induces Heterodimerization of cRaf and BRaf
  publication-title: Cancer Res.
– volume: 380
  start-page: 358
  year: 2012
  ident: ref_11
  article-title: Dabrafenib in BRAF-Mutated Metastatic Melanoma: A Multicentre, Open-Label, Phase 3 Randomised Controlled Trial
  publication-title: Lancet
  doi: 10.1016/S0140-6736(12)60868-X
– volume: 333
  start-page: 1300
  year: 2011
  ident: ref_128
  article-title: Tet Proteins can Convert 5-Methylcytosine to 5-Formylcytosine and 5-Carboxylcytosine
  publication-title: Science
  doi: 10.1126/science.1210597
– volume: 107
  start-page: 15449
  year: 2010
  ident: ref_159
  article-title: Core Epithelial-to-Mesenchymal Transition Interactome Gene-Expression Signature is Associated with Claudin-Low and Metaplastic Breast Cancer Subtypes
  publication-title: Proc. Natl. Acad. Sci. USA
  doi: 10.1073/pnas.1004900107
– volume: 410
  start-page: 37
  year: 2001
  ident: ref_53
  article-title: Mammalian MAP Kinase Signalling Cascades
  publication-title: Nature
  doi: 10.1038/35065000
– volume: 371
  start-page: 1877
  year: 2014
  ident: ref_100
  article-title: Combined BRAF and MEK Inhibition Versus BRAF Inhibition Alone in Melanoma
  publication-title: N. Engl. J. Med.
  doi: 10.1056/NEJMoa1406037
– volume: 363
  start-page: 1150
  year: 2019
  ident: ref_113
  article-title: Tissue-Specificity in Cancer: The Rule, Not the Exception
  publication-title: Science
  doi: 10.1126/science.aaw3472
– volume: 33
  start-page: 561
  year: 2001
  ident: ref_148
  article-title: Expression of mRNA for DNA Methyltransferases and Methyl-CpG-Binding Proteins and DNA Methylation Status on CpG Islands and Pericentromeric Satellite Regions During Human Hepatocarcinogenesis
  publication-title: Hepatology
  doi: 10.1053/jhep.2001.22507
– volume: 106
  start-page: 20411
  year: 2009
  ident: ref_104
  article-title: MEK1 Mutations Confer Resistance to MEK and B-RAF Inhibition
  publication-title: Proc. Natl. Acad. Sci. USA
  doi: 10.1073/pnas.0905833106
– volume: 25
  start-page: 284
  year: 2019
  ident: ref_97
  article-title: RAF Inhibitor PLX8394 Selectively Disrupts BRAF Dimers and RAS-Independent BRAF-Mutant-Driven Signaling
  publication-title: Nat. Med.
  doi: 10.1038/s41591-018-0274-5
– volume: 19
  start-page: 603
  year: 2018
  ident: ref_87
  article-title: Encorafenib Plus Binimetinib Versus Vemurafenib or Encorafenib in Patients with BRAF-Mutant Melanoma (COLUMBUS): A Multicentre, Open-Label, Randomised Phase 3 Trial
  publication-title: Lancet Oncol.
  doi: 10.1016/S1470-2045(18)30142-6
– volume: 27
  start-page: 574
  year: 2015
  ident: ref_42
  article-title: Intravital Imaging Reveals How BRAF Inhibition Generates Drug-Tolerant Microenvironments with High Integrin β1/FAK Signaling
  publication-title: Cancer Cell
  doi: 10.1016/j.ccell.2015.03.008
– volume: 39
  start-page: D945
  year: 2011
  ident: ref_79
  article-title: COSMIC: Mining Complete Cancer Genomes in the Catalogue of Somatic Mutations in Cancer
  publication-title: Nucleic Acids Res.
  doi: 10.1093/nar/gkq929
– volume: 11
  start-page: 797
  year: 2015
  ident: ref_38
  article-title: Systematic Analysis of BRAF(V600E) Melanomas Reveals a Role for JNK/c-Jun Pathway in Adaptive Resistance to Drug-Induced Apoptosis
  publication-title: Mol. Syst. Biol.
  doi: 10.15252/msb.20145877
– volume: 41
  start-page: 178
  year: 2009
  ident: ref_134
  article-title: The Human Colon Cancer Methylome Shows Similar Hypo- and Hypermethylation at Conserved Tissue-Specific CpG Island Shores
  publication-title: Nat. Genet.
  doi: 10.1038/ng.298
– volume: 34
  start-page: 4448
  year: 2015
  ident: ref_31
  article-title: A Stress-Induced Early Innate Response Causes Multidrug Tolerance in Melanoma
  publication-title: Oncogene
  doi: 10.1038/onc.2014.372
– volume: 366
  start-page: 707
  year: 2012
  ident: ref_3
  article-title: Survival in BRAF V600-Mutant Advanced Melanoma Treated with Vemurafenib
  publication-title: N. Engl. J. Med.
  doi: 10.1056/NEJMoa1112302
– volume: 372
  start-page: 30
  year: 2015
  ident: ref_8
  article-title: Improved Overall Survival in Melanoma with Combined Dabrafenib and Trametinib
  publication-title: N. Engl. J. Med.
  doi: 10.1056/NEJMoa1412690
– volume: 5
  start-page: 5694
  year: 2014
  ident: ref_22
  article-title: Increased MAPK Reactivation in Early Resistance to Dabrafenib/Trametinib Combination Therapy of BRAF-Mutant Metastatic Melanoma
  publication-title: Nat. Commun.
  doi: 10.1038/ncomms6694
– volume: 31
  start-page: 2629
  year: 2012
  ident: ref_69
  article-title: Distinct Requirement for An Intact Dimer Interface in Wild-Type, V600E and Kinase-Dead B-Raf Signalling
  publication-title: EMBO J.
  doi: 10.1038/emboj.2012.100
– volume: 3
  start-page: 158
  year: 2013
  ident: ref_108
  article-title: Inhibiting EGF Receptor or SRC Family Kinase Signaling Overcomes BRAF Inhibitor Resistance in Melanoma
  publication-title: Cancer Discov.
  doi: 10.1158/2159-8290.CD-12-0386
– volume: 352
  start-page: 189
  year: 2016
  ident: ref_46
  article-title: Dissecting the Multicellular Ecosystem of Metastatic Melanoma by Single-Cell RNA-seq
  publication-title: Science
  doi: 10.1126/science.aad0501
– volume: 30
  start-page: 485
  year: 2016
  ident: ref_94
  article-title: An Integrated Model of RAF Inhibitor Action Predicts Inhibitor Activity against Oncogenic BRAF Signaling
  publication-title: Cancer Cell
  doi: 10.1016/j.ccell.2016.06.024
– volume: 9
  start-page: 329
  year: 2019
  ident: ref_88
  article-title: Targeting Alterations in the RAF-MEK Pathway
  publication-title: Cancer Discov.
  doi: 10.1158/2159-8290.CD-18-1321
– volume: 19
  start-page: 4532
  year: 2013
  ident: ref_62
  article-title: Clinical, Pathologic, and Biologic Features Associated with BRAF Mutations in Non-Small Cell Lung Cancer
  publication-title: Clin. Cancer Res.
  doi: 10.1158/1078-0432.CCR-13-0657
– volume: 548
  start-page: 239
  year: 2017
  ident: ref_76
  article-title: A Braf Kinase-Inactive Mutant Induces Lung Adenocarcinoma
  publication-title: Nature
  doi: 10.1038/nature23297
– volume: 373
  start-page: 726
  year: 2015
  ident: ref_4
  article-title: Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations
  publication-title: N. Engl. J. Med.
  doi: 10.1056/NEJMoa1502309
– volume: 6
  start-page: 6051
  year: 2015
  ident: ref_168
  article-title: The Epigenetic Modifier EZH2 Controls Melanoma Growth and Metastasis through Silencing of Distinct Tumour Suppressors
  publication-title: Nat. Commun.
  doi: 10.1038/ncomms7051
– volume: 173
  start-page: 499
  year: 2018
  ident: ref_114
  article-title: Profound Tissue Specificity in Proliferation Control Underlies Cancer Drivers and Aneuploidy Patterns
  publication-title: Cell
  doi: 10.1016/j.cell.2018.02.037
– volume: 435
  start-page: 1262
  year: 2005
  ident: ref_153
  article-title: Global Histone Modification Patterns Predict Risk of Prostate Cancer Recurrence
  publication-title: Nature
  doi: 10.1038/nature03672
– volume: 24
  start-page: 268
  year: 2006
  ident: ref_167
  article-title: EZH2 Expression is Associated with High Proliferation Rate and Aggressive Tumor Subgroups in Cutaneous Melanoma and Cancers of the Endometrium, Prostate, and Breast
  publication-title: J. Clin. Oncol.
  doi: 10.1200/JCO.2005.01.5180
– volume: 367
  start-page: 1694
  year: 2012
  ident: ref_13
  article-title: Combined BRAF and MEK Inhibition in Melanoma with BRAF V600 Mutations
  publication-title: N. Engl. J. Med.
  doi: 10.1056/NEJMoa1210093
– volume: 364
  start-page: 2507
  year: 2011
  ident: ref_7
  article-title: Improved Survival with Vemurafenib in Melanoma with BRAF V600E Mutation
  publication-title: N. Engl. J. Med.
  doi: 10.1056/NEJMoa1103782
– volume: 38
  start-page: 4384
  year: 2019
  ident: ref_169
  article-title: An Actionable Axis Linking NFATc2 to EZH2 Controls the EMT-Like Program of Melanoma Cells
  publication-title: Oncogene
  doi: 10.1038/s41388-019-0729-2
– volume: 8
  start-page: 2651
  year: 1988
  ident: ref_81
  article-title: B-raf, a New Member of the Raf Family, is Activated by DNA Rearrangement
  publication-title: Mol. Cell. Biol.
– volume: 53
  start-page: 1137
  year: 2004
  ident: ref_144
  article-title: BRAF Mutation is Associated with DNA Methylation in Serrated Polyps and Cancers of the Colorectum
  publication-title: Gut
  doi: 10.1136/gut.2003.037671
– ident: ref_84
  doi: 10.1371/journal.pone.0015588
– volume: 366
  start-page: 207
  year: 2012
  ident: ref_90
  article-title: RAS Mutations in Cutaneous Squamous-Cell Carcinomas in Patients Treated with BRAF Inhibitors
  publication-title: N. Engl. J. Med.
  doi: 10.1056/NEJMoa1105358
– volume: 508
  start-page: 118
  year: 2014
  ident: ref_36
  article-title: Reversible and Adaptive Resistance to BRAF(V600E) Inhibition in Melanoma
  publication-title: Nature
  doi: 10.1038/nature13121
– volume: 547
  start-page: 453
  year: 2017
  ident: ref_115
  article-title: Dependency of a Therapy-Resistant State of Cancer Cells on a Lipid Peroxidase Pathway
  publication-title: Nature
  doi: 10.1038/nature23007
– volume: 29
  start-page: 2046
  year: 2011
  ident: ref_63
  article-title: Clinical Characteristics of Patients with Lung Adenocarcinomas Harboring BRAF Mutations
  publication-title: J. Clin. Oncol.
  doi: 10.1200/JCO.2010.33.1280
– volume: 113
  start-page: 1250
  year: 2016
  ident: ref_146
  article-title: Common BRAF(V600E)-Directed Pathway Mediates Widespread Epigenetic Silencing in Colorectal Cancer and Melanoma
  publication-title: Proc. Natl. Acad. Sci. USA
  doi: 10.1073/pnas.1525619113
– volume: 526
  start-page: 583
  year: 2015
  ident: ref_96
  article-title: RAF Inhibitors that Evade Paradoxical MAPK Pathway Activation
  publication-title: Nature
  doi: 10.1038/nature14982
– ident: ref_102
  doi: 10.1371/journal.pone.0085004
– volume: 386
  start-page: 444
  year: 2015
  ident: ref_101
  article-title: Dabrafenib and Trametinib Versus Dabrafenib and Placebo for Val600 BRAF-Mutant Melanoma: A Multicentre, Double-Blind, Phase 3 Randomised Controlled Trial
  publication-title: Lancet
  doi: 10.1016/S0140-6736(15)60898-4
– volume: 357
  start-page: eaal2380
  year: 2017
  ident: ref_49
  article-title: Epigenetic Plasticity and the Hallmarks of Cancer
  publication-title: Science
  doi: 10.1126/science.aal2380
– volume: 22
  start-page: 262
  year: 2016
  ident: ref_51
  article-title: Tumor Cells can Follow Distinct Evolutionary Paths to Become Resistant to Epidermal Growth Factor Receptor Inhibition
  publication-title: Nat. Med.
  doi: 10.1038/nm.4040
– volume: 71
  start-page: 7360
  year: 2011
  ident: ref_137
  article-title: 5-Hydroxymethylcytosine is Strongly Depleted in Human Cancers But Its Levels Do Not Correlate with IDH1 Mutations
  publication-title: Cancer Res.
  doi: 10.1158/0008-5472.CAN-11-2023
– volume: 153
  start-page: 38
  year: 2013
  ident: ref_154
  article-title: Interplay Between the Cancer Genome and Epigenome
  publication-title: Cell
  doi: 10.1016/j.cell.2013.03.008
– ident: ref_74
  doi: 10.1186/s12885-015-1811-y
– volume: 17
  start-page: 989
  year: 2011
  ident: ref_99
  article-title: GSK1120212 (JTP-74057) is an Inhibitor of MEK Activity and Activation with Favorable Pharmacokinetic Properties for Sustained in vivo Pathway Inhibition
  publication-title: Clin. Cancer Res.
  doi: 10.1158/1078-0432.CCR-10-2200
– volume: 9
  start-page: 1011
  year: 2017
  ident: ref_121
  article-title: Targeting Endothelin Receptor Signalling Overcomes Heterogeneity Driven Therapy Failure
  publication-title: EMBO Mol. Med.
  doi: 10.15252/emmm.201607156
– volume: 47
  start-page: 250
  year: 2015
  ident: ref_161
  article-title: The Hippo Effector YAP Promotes Resistance to RAF- and MEK-Targeted Cancer Therapies
  publication-title: Nat. Genet.
  doi: 10.1038/ng.3218
– volume: 13
  start-page: 928
  year: 2014
  ident: ref_110
  article-title: Targeting RAS-ERK Signalling in Cancer: Promises and Challenges
  publication-title: Nat. Rev. Drug. Discov.
  doi: 10.1038/nrd4281
– volume: 71
  start-page: 2750
  year: 2011
  ident: ref_106
  article-title: PTEN Loss Confers BRAF Inhibitor Resistance to Melanoma Cells through the Suppression of BIM Expression
  publication-title: Cancer Res.
  doi: 10.1158/0008-5472.CAN-10-2954
– volume: 65
  start-page: 9719
  year: 2005
  ident: ref_78
  article-title: Mutations of C-RAF are Rare in Human Cancer Because C-RAF Has a Low Basal Kinase Activity Compared with B-RAF
  publication-title: Cancer Res.
  doi: 10.1158/0008-5472.CAN-05-1683
– volume: 24
  start-page: 1599
  year: 2018
  ident: ref_162
  article-title: Transcriptional Addiction in Cancer Cells is Mediated by YAP/TAZ through BRD4
  publication-title: Nat. Med.
  doi: 10.1038/s41591-018-0158-8
– volume: 480
  start-page: 387
  year: 2011
  ident: ref_17
  article-title: RAF Inhibitor Resistance is Mediated by Dimerization of Aberrantly Spliced BRAF(V600E)
  publication-title: Nature
  doi: 10.1038/nature10662
– volume: 22
  start-page: 668
  year: 2012
  ident: ref_37
  article-title: Relief of Profound Feedback Inhibition of Mitogenic Signaling by RAF Inhibitors Attenuates Their Activity in BRAFV600E Melanomas
  publication-title: Cancer Cell
  doi: 10.1016/j.ccr.2012.10.009
– volume: 468
  start-page: 973
  year: 2010
  ident: ref_16
  article-title: Melanomas Acquire Resistance to B-RAF(V600E) Inhibition by RTK or N-RAS upregulation
  publication-title: Nature
  doi: 10.1038/nature09626
– volume: 6
  start-page: 300
  year: 2016
  ident: ref_82
  article-title: Oncogenic BRAF Deletions That Function as Homodimers and Are Sensitive to Inhibition by RAF Dimer Inhibitor LY3009120
  publication-title: Cancer Discov.
  doi: 10.1158/2159-8290.CD-15-0896
– volume: 7
  start-page: 10690
  year: 2016
  ident: ref_52
  article-title: Diverse Drug-Resistance Mechanisms can Emerge from Drug-Tolerant Cancer Persister Cells
  publication-title: Nat. Commun.
  doi: 10.1038/ncomms10690
– volume: 333
  start-page: 1303
  year: 2011
  ident: ref_131
  article-title: Tet-Mediated Formation of 5-Carboxylcytosine and Its Excision by TDG in Mammalian DNA
  publication-title: Science
  doi: 10.1126/science.1210944
– volume: 464
  start-page: 431
  year: 2010
  ident: ref_92
  article-title: RAF Inhibitors Prime Wild-Type RAF to Activate the MAPK Pathway and Enhance Growth
  publication-title: Nature
  doi: 10.1038/nature08833
– volume: 173
  start-page: 371
  year: 2018
  ident: ref_1
  article-title: Comprehensive Characterization of Cancer Driver Genes and Mutations
  publication-title: Cell
  doi: 10.1016/j.cell.2018.02.060
– volume: 141
  start-page: 583
  year: 2010
  ident: ref_28
  article-title: A Temporarily Distinct Subpopulation of Slow-Cycling Melanoma Cells is Required for Continuous Tumor Growth
  publication-title: Cell
  doi: 10.1016/j.cell.2010.04.020
– volume: 462
  start-page: 315
  year: 2009
  ident: ref_136
  article-title: Human DNA Methylomes at Base Resolution Show Widespread Epigenomic Differences
  publication-title: Nature
  doi: 10.1038/nature08514
– volume: 106
  start-page: dju106
  year: 2014
  ident: ref_65
  article-title: Patient and Tumor Characteristics and BRAF and KRAS Mutations in Colon Cancer, NCCTG/Alliance N0147
  publication-title: J. Natl. Cancer Inst.
  doi: 10.1093/jnci/dju106
– volume: 49
  start-page: 751
  year: 2013
  ident: ref_70
  article-title: Effects of Raf Dimerization and Its Inhibition on Normal and Disease-Associated Raf Signaling
  publication-title: Mol. Cell
  doi: 10.1016/j.molcel.2012.12.018
– volume: 102
  start-page: 18
  year: 2011
  ident: ref_141
  article-title: Two Groups of DNA Methylation Markers to Classify Colorectal Cancer into Three Epigenotypes
  publication-title: Cancer Sci.
  doi: 10.1111/j.1349-7006.2010.01712.x
– volume: 464
  start-page: 427
  year: 2010
  ident: ref_93
  article-title: RAF Inhibitors Transactivate RAF Dimers and ERK Signalling in Cells With Wild-Type BRAF
  publication-title: Nature
  doi: 10.1038/nature08902
– volume: 27
  start-page: 1318
  year: 2013
  ident: ref_152
  article-title: A Double Take on Bivalent Promoters
  publication-title: Genes Dev.
  doi: 10.1101/gad.219626.113
– volume: 25
  start-page: 697
  year: 2014
  ident: ref_98
  article-title: Disruption of CRAF-Mediated MEK Activation is Required for Effective MEK Inhibition in KRAS Mutant Tumors
  publication-title: Cancer Cell
  doi: 10.1016/j.ccr.2014.03.011
– volume: 417
  start-page: 949
  year: 2002
  ident: ref_57
  article-title: Mutations of the BRAF Gene in Human Cancer
  publication-title: Nature
  doi: 10.1038/nature00766
– volume: 47
  start-page: 193
  year: 2015
  ident: ref_160
  article-title: YAP and the Drug Resistance Highway
  publication-title: Nat. Genet.
  doi: 10.1038/ng.3228
– volume: 490
  start-page: 412
  year: 2012
  ident: ref_124
  article-title: Melanomas Resist T-cell Therapy Through Inflammation-Induced Reversible Dedifferentiation
  publication-title: Nature
  doi: 10.1038/nature11538
– volume: 10
  start-page: e8446
  year: 2018
  ident: ref_164
  article-title: Co-Targeting BET and MEK As Salvage Therapy for MAPK and Checkpoint Inhibitor-Resistant Melanoma
  publication-title: EMBO Mol. Med.
  doi: 10.15252/emmm.201708446
– volume: 467
  start-page: 596
  year: 2010
  ident: ref_86
  article-title: Clinical Efficacy of a RAF Inhibitor Needs Broad Target Blockade in BRAF-Mutant Melanoma
  publication-title: Nature
  doi: 10.1038/nature09454
– volume: 18
  start-page: 683
  year: 2010
  ident: ref_107
  article-title: Acquired Resistance to BRAF Inhibitors Mediated by a RAF Kinase Switch in Melanoma can be Overcome by Cotargeting MEK and IGF-1R/PI3K
  publication-title: Cancer Cell
  doi: 10.1016/j.ccr.2010.11.023
– volume: 551
  start-page: 247
  year: 2017
  ident: ref_118
  article-title: Drug-Tolerant Persister Cancer Cells are Vulnerable to GPX4 Inhibition
  publication-title: Nature
  doi: 10.1038/nature24297
– volume: 162
  start-page: 1271
  year: 2015
  ident: ref_15
  article-title: Non-genomic and Immune Evolution of Melanoma Acquiring MAPKi Resistance
  publication-title: Cell
  doi: 10.1016/j.cell.2015.07.061
– volume: 15
  start-page: 327
  year: 2015
  ident: ref_39
  article-title: Phosphoproteomic Analysis of Basal and Therapy-Induced Adaptive Signaling Networks in BRAF and NRAS Mutant Melanoma
  publication-title: Proteomics
  doi: 10.1002/pmic.201400200
– volume: 155
  start-page: 462
  year: 2013
  ident: ref_67
  article-title: The Somatic Genomic Landscape of Glioblastoma
  publication-title: Cell
  doi: 10.1016/j.cell.2013.09.034
– volume: 548
  start-page: 234
  year: 2017
  ident: ref_72
  article-title: Tumours with Class 3 BRAF Mutants Are Sensitive to the Inhibition of Activated RAS
  publication-title: Nature
  doi: 10.1038/nature23291
– volume: 1
  start-page: 686
  year: 1995
  ident: ref_139
  article-title: 5′ CpG Island Methylation is Associated with Transcriptional Silencing of the Tumour Suppressor p16/CDKN2/MTS1 in Human Cancers
  publication-title: Nat. Med.
  doi: 10.1038/nm0795-686
– volume: 33
  start-page: 162
  year: 2018
  ident: ref_158
  article-title: An Epigenetic Switch: From Senescent Melanocytes to Malignant Melanoma (and Back)
  publication-title: Cancer Cell
  doi: 10.1016/j.ccell.2018.01.013
– volume: 97
  start-page: 649
  year: 2017
  ident: ref_122
  article-title: The Master Role of Microphthalmia-Associated Transcription Factor in Melanocyte and Melanoma Biology
  publication-title: Lab. Investig.
  doi: 10.1038/labinvest.2017.9
– volume: 13
  start-page: 905
  year: 2017
  ident: ref_35
  article-title: Adaptive Resistance of Melanoma Cells to RAF Inhibition Via Reversible Induction of a Slowly Dividing De-Differentiated State
  publication-title: Mol. Syst. Biol.
  doi: 10.15252/msb.20166796
– volume: 274
  start-page: 7936
  year: 1999
  ident: ref_165
  article-title: Ras Proteins Induce Senescence by Altering the Intracellular Levels of Reactive Oxygen Species
  publication-title: J. Biol. Chem.
  doi: 10.1074/jbc.274.12.7936
– volume: 140
  start-page: 209
  year: 2010
  ident: ref_73
  article-title: Kinase-Dead BRAF and Oncogenic RAS Cooperate to Drive Tumor Progression Through CRAF
  publication-title: Cell
  doi: 10.1016/j.cell.2009.12.040
– ident: ref_60
  doi: 10.1038/nature13385
– volume: 124
  start-page: 1582
  year: 2014
  ident: ref_77
  article-title: Oncogenic and Sorafenib-Sensitive ARAF Mutations in Lung Adenocarcinoma
  publication-title: J. Clin. Investig.
  doi: 10.1172/JCI72763
– volume: 9
  start-page: 526
  year: 2019
  ident: ref_166
  article-title: MAPK Pathway Suppression Unmasks Latent DNA Repair Defects and Confers a Chemical Synthetic Vulnerability in BRAF-, NRAS-, and NF1-Mutant Melanomas
  publication-title: Cancer Discov.
  doi: 10.1158/2159-8290.CD-18-0879
– volume: 70
  start-page: 8736
  year: 2010
  ident: ref_40
  article-title: Basal and Treatment-Induced Activation of AKT Mediates Resistance to Cell Death by AZD6244 (ARRY-142886) in Braf-Mutant Human Cutaneous Melanoma Cells
  publication-title: Cancer Res.
  doi: 10.1158/0008-5472.CAN-10-0902
– volume: 5
  start-page: 1183
  year: 2016
  ident: ref_163
  article-title: BET and BRAF Inhibitors Act Synergistically Against BRAF-Mutant Melanoma
  publication-title: Cancer Med.
  doi: 10.1002/cam4.667
– volume: 174
  start-page: 843
  year: 2018
  ident: ref_26
  article-title: Toward Minimal Residual Disease-Directed Therapy in Melanoma
  publication-title: Cell
  doi: 10.1016/j.cell.2018.06.025
– volume: 141
  start-page: 69
  year: 2010
  ident: ref_32
  article-title: A Chromatin-Mediated Reversible Drug-Tolerant State in Cancer Cell Subpopulations
  publication-title: Cell
  doi: 10.1016/j.cell.2010.02.027
– volume: 26
  start-page: 3279
  year: 2007
  ident: ref_54
  article-title: MAP Kinase Signalling Pathways in Cancer
  publication-title: Oncogene
  doi: 10.1038/sj.onc.1210421
– volume: 28
  start-page: 370
  year: 2015
  ident: ref_95
  article-title: BRAF Mutants Evade ERK-Dependent Feedback by Different Mechanisms that Determine Their Sensitivity to Pharmacologic Inhibition
  publication-title: Cancer Cell
  doi: 10.1016/j.ccell.2015.08.001
– volume: 5
  start-page: 358
  year: 2015
  ident: ref_103
  article-title: Clinical Acquired Resistance to RAF Inhibitor Combinations in BRAF-Mutant Colorectal Cancer through MAPK Pathway Alterations
  publication-title: Cancer Discov.
  doi: 10.1158/2159-8290.CD-14-1518
– volume: 16
  start-page: 549
  year: 2019
  ident: ref_126
  article-title: Cell-State Dynamics and Therapeutic Resistance in Melanoma from the Perspective of MITF and IFNγ Pathways
  publication-title: Nat. Rev. Clin. Oncol.
  doi: 10.1038/s41571-019-0204-6
– volume: 38
  start-page: 787
  year: 2006
  ident: ref_143
  article-title: CpG Island Methylator Phenotype Underlies Sporadic Microsatellite Instability and is Tightly Associated with BRAF Mutation in Colorectal Cancer
  publication-title: Nat. Genet.
  doi: 10.1038/ng1834
– volume: 4
  start-page: 69
  year: 2014
  ident: ref_23
  article-title: A Novel AKT1 Mutant Amplifies An Adaptive Melanoma Response to BRAF Inhibition
  publication-title: Cancer Discov.
  doi: 10.1158/2159-8290.CD-13-0279
– volume: 37
  start-page: 302
  year: 2018
  ident: ref_27
  article-title: A Slow-Cycling Subpopulation of Melanoma Cells with Highly Invasive Properties
  publication-title: Oncogene
  doi: 10.1038/onc.2017.341
– volume: 5
  start-page: 5712
  year: 2014
  ident: ref_44
  article-title: Low MITF/AXL Ratio Predicts Early Resistance to Multiple Targeted Drugs In Melanoma
  publication-title: Nat. Commun.
  doi: 10.1038/ncomms6712
– volume: 31
  start-page: 24
  year: 2018
  ident: ref_64
  article-title: Molecular Testing for BRAF Mutations to Inform Melanoma Treatment Decisions: A Move toward Precision Medicine
  publication-title: Mod. Pathol.
  doi: 10.1038/modpathol.2017.104
– volume: 29
  start-page: 270
  year: 2016
  ident: ref_24
  article-title: Inhibiting Drivers of Non-Mutational Drug Tolerance Is a Salvage Strategy for Targeted Melanoma Therapy
  publication-title: Cancer Cell
  doi: 10.1016/j.ccell.2016.02.003
– volume: 63
  start-page: 1454
  year: 2003
  ident: ref_58
  article-title: High prevalence of BRAF mutations in thyroid cancer: Genetic Evidence for Constitutive Activation of the RET/PTC-RAS-BRAF Signaling Pathway in Papillary Thyroid Carcinoma
  publication-title: Cancer Res.
– volume: 105
  start-page: 3041
  year: 2008
  ident: ref_85
  article-title: Discovery of a Selective Inhibitor of Oncogenic B-Raf Kinase with Potent Antimelanoma Activity
  publication-title: Proc. Natl. Acad. Sci. USA
  doi: 10.1073/pnas.0711741105
– volume: 445
  start-page: 843
  year: 2007
  ident: ref_123
  article-title: Melanocyte Biology and Skin Pigmentation
  publication-title: Nature
  doi: 10.1038/nature05660
– volume: 36
  start-page: 3477
  year: 2018
  ident: ref_68
  article-title: BRAF Inhibition in BRAFV600-Mutant Gliomas: Results From the VE-BASKET Study
  publication-title: J. Clin. Oncol.
  doi: 10.1200/JCO.2018.78.9990
– volume: 22
  start-page: 472
  year: 2016
  ident: ref_6
  article-title: A Framework for Understanding and Targeting Residual Disease in Oncogene-Driven Solid Cancers
  publication-title: Nat. Med.
  doi: 10.1038/nm.4091
– volume: 116
  start-page: 855
  year: 2004
  ident: ref_71
  article-title: Mechanism of Activation of the RAF-ERK Signaling Pathway by Oncogenic Mutations of B-RAF
  publication-title: Cell
  doi: 10.1016/S0092-8674(04)00215-6
– volume: 471
  start-page: 513
  year: 2011
  ident: ref_157
  article-title: The Histone Methyltransferase SETDB1 is Recurrently Amplified in Melanoma and Accelerates Its Onset
  publication-title: Nature
  doi: 10.1038/nature09806
– volume: 3
  start-page: 1140
  year: 2013
  ident: ref_125
  article-title: Modeling Neural Crest Induction, Melanocyte Specification, and Disease-Related Pigmentation Defects in hESCs and Patient-Specific iPSCs
  publication-title: Cell Rep.
  doi: 10.1016/j.celrep.2013.03.025
– volume: 293
  start-page: 1074
  year: 2001
  ident: ref_151
  article-title: Translating the Histone Code
  publication-title: Science
  doi: 10.1126/science.1063127
– volume: 33
  start-page: 322
  year: 2018
  ident: ref_48
  article-title: Targeting the Senescence-Overriding Cooperative Activity of Structurally Unrelated H3K9 Demethylases in Melanoma
  publication-title: Cancer Cell
  doi: 10.1016/j.ccell.2018.01.002
– volume: 23
  start-page: 811
  year: 2013
  ident: ref_29
  article-title: Overcoming Intrinsic Multidrug Resistance in Melanoma by Blocking the Mitochondrial Respiratory Chain of Slow-Cycling JARID1B(high) Cells
  publication-title: Cancer Cell
  doi: 10.1016/j.ccr.2013.05.003
– volume: 29
  start-page: 3085
  year: 2011
  ident: ref_18
  article-title: Dissecting Therapeutic Resistance to RAF Inhibition in Melanoma by Tumor Genomic Profiling
  publication-title: J. Clin. Oncol.
  doi: 10.1200/JCO.2010.33.2312
– volume: 111
  start-page: E748
  year: 2014
  ident: ref_30
  article-title: Mapping the Molecular Determinants of BRAF Oncogene Dependence in Human Lung Cancer
  publication-title: Proc. Natl. Acad. Sci. USA
  doi: 10.1073/pnas.1320956111
– volume: 44
  start-page: 760
  year: 2012
  ident: ref_155
  article-title: Whole-Genome Sequencing of Liver Cancers Identifies Etiological Influences on Mutation Patterns and Recurrent Mutations in Chromatin Regulators
  publication-title: Nat. Genet.
  doi: 10.1038/ng.2291
– volume: 3
  start-page: 350
  year: 2013
  ident: ref_105
  article-title: A Genome-Scale RNA Interference Screen Implicates NF1 Loss in Resistance to RAF Inhibition
  publication-title: Cancer Discov.
  doi: 10.1158/2159-8290.CD-12-0470
– volume: 9
  start-page: 3440
  year: 2018
  ident: ref_116
  article-title: SIRT6 Haploinsufficiency Induces BRAFV600E Melanoma Cell Resistance to MAPK Inhibitors Via IGF Signalling
  publication-title: Nat. Commun.
  doi: 10.1038/s41467-018-05966-z
– volume: 504
  start-page: 138
  year: 2013
  ident: ref_43
  article-title: A Melanocyte Lineage Program Confers Resistance to MAP Kinase Pathway Inhibition
  publication-title: Nature
  doi: 10.1038/nature12688
– volume: 33
  start-page: 890
  year: 2018
  ident: ref_5
  article-title: Multi-stage Differentiation Defines Melanoma Subtypes with Differential Vulnerability to Drug-Induced Iron-Dependent Oxidative Stress
  publication-title: Cancer Cell
  doi: 10.1016/j.ccell.2018.03.017
– volume: 3
  start-page: 448
  year: 2006
  ident: ref_2
  article-title: Mechanisms of disease: Oncogene Addiction—A Rationale for Molecular Targeting in Cancer Therapy
  publication-title: Nat. Clin. Pract. Oncol
  doi: 10.1038/ncponc0558
– volume: 27
  start-page: 240
  year: 2015
  ident: ref_21
  article-title: Tunable-Combinatorial Mechanisms of Acquired Resistance Limit the Efficacy of BRAF/MEK Cotargeting But Result in Melanoma Drug Addiction
  publication-title: Cancer Cell
  doi: 10.1016/j.ccell.2014.11.018
– volume: 114
  start-page: 13679
  year: 2017
  ident: ref_34
  article-title: Single-Cell Analysis Resolves the Cell State Transition and Signaling Dynamics Associated with Melanoma Drug-Induced Resistance
  publication-title: Proc. Natl. Acad. Sci. USA
  doi: 10.1073/pnas.1712064115
– volume: 8
  start-page: 417
  year: 2018
  ident: ref_9
  article-title: Convergent Therapeutic Strategies to Overcome the Heterogeneity of Acquired Resistance in BRAFV600E Colorectal Cancer
  publication-title: Cancer Discov.
  doi: 10.1158/2159-8290.CD-17-1227
– volume: 25
  start-page: 1010
  year: 2011
  ident: ref_133
  article-title: CpG Islands and the Regulation of Transcription
  publication-title: Genes Dev.
  doi: 10.1101/gad.2037511
– volume: 19
  start-page: 377
  year: 2019
  ident: ref_120
  article-title: Phenotype Plasticity As Enabler of Melanoma Progression and Therapy Resistance
  publication-title: Nat. Rev. Cancer
  doi: 10.1038/s41568-019-0154-4
– volume: 4
  start-page: 816
  year: 2014
  ident: ref_45
  article-title: A Melanoma Cell State Distinction Influences Sensitivity to MAPK Pathway Inhibitors
  publication-title: Cancer Discov.
  doi: 10.1158/2159-8290.CD-13-0424
– volume: 4
  start-page: 94
  year: 2014
  ident: ref_20
  article-title: The Genetic Landscape of Clinical Resistance to RAF Inhibition in Metastatic Melanoma
  publication-title: Cancer Discov.
  doi: 10.1158/2159-8290.CD-13-0617
– volume: 520
  start-page: 368
  year: 2015
  ident: ref_41
  article-title: Therapy-Induced Tumour Secretomes Promote Resistance and Tumour Progression
  publication-title: Nature
  doi: 10.1038/nature14336
SSID ssj0000331767
Score 2.3260477
SecondaryResourceType review_article
Snippet About eight percent of all human tumors (including 50% of melanomas) carry gain-of-function mutations in the BRAF oncogene. Mutated BRAF and subsequent...
SourceID unpaywall
pubmedcentral
proquest
crossref
SourceType Open Access Repository
Aggregation Database
Enrichment Source
Index Database
StartPage 1480
SubjectTerms Cancer
Cloning
DNA methylation
Drug resistance
Epigenetics
Gene expression
Gene regulation
Genotype & phenotype
Histones
Kinases
MAP kinase
Melanoma
Mutants
Mutation
Oncogenes
Ovaries
Proteins
Response rates
Review
Signal transduction
Thyroid gland
Tumors
SummonAdditionalLinks – databaseName: ProQuest Central
  dbid: BENPR
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwhV3da9swED-6FLa9lHYfzP1ChT1sD16VSJbshzLaNaEUko2yQt-MPmkhs7M6ofS_38mx3aXQ9sUYJGP5ztLdT7r7HcBnpvvcpgMba-VZzI31sTYpAldLpeEZc74m0xlPxNklP79KrtZg0ubChLDKdk2sF2pbmrBHfohARiZonhP6ffY3DlWjwulqW0JDNaUV7FFNMfYK1sOSzHuwfjKc_Lrodl0oQ3sp5JLjhyHePzRBuLcVTvmwt0ZXzdODz_k4YvLNopip-zs1nf5njkabsNH4keR4qfgtWHPFO3g9bk7K38PRcBZ4NkOKIhm7kN57U_2pSOnJsAoxTyTklZCTi-MR-VmYMnQlp01BXHP_AS5Hw98_zuKmVEJsuODzONOJoolXLPH91PQd3vJMZjaj2mu8aJ8Z4xALGvRYHBVKSubxey26W5Qrxz5CrygL9wmIsNQPlBWIVbCFSS1T1c8Sa6xGaJfQCL61EspNwyMeyllMc8QTQaT5I5FG8KV7YLak0Hi6624r8ryZS1X-oPkIDrpmnAXhaEMVrlxgnxoZonM6iECuqKp7ZeDRXm0pbq5rPm2BEEuINIKvnVJfGuj28wPdgbfoWGXLoL9d6M1vF24PnZe53m_-yH-CCfFW
  priority: 102
  providerName: ProQuest
– databaseName: Scholars Portal Open Access Journals
  dbid: M48
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjV1da9swFBVrBm1fxtZuLF06NCijfXAn27JkPZTSbQllkBVKA30z-mSF1EnjhC7_fvc6TtqUju3FGCTb8pVknWNJ5xBykJqYuzxxkdEhjbh1ITI2B-LqmLRcpT7UYjr9n-J8wH9cZ9cPVqVNAKtnqR36SQ0mw-Pfd_NT6PAnyDiBsn-xGJ9JBb0Wf4-xz-O7CF2lcPa1sdjYIC9hpIpRW7_fwP_6S53C6FmbzCZMJpEQii_Uf5677frA9YBGn66l3JqVYz2_18Pho4Gq95q8ahAmPVs0iTfkhS93yGa_mUPfJSfdMSpw4uZF2ve48femuq3oKNBuhauhKO44oV8vz3r0orQjzEq_N1a5dv6WDHrdq2_nUWOiEFku-DRSJtMsCzrNQpzb2MMpV1I5xUwwcDBBWeuBJVrAMp4JLWUa4H0dADHGtU_fkVY5Kv17QoVjIdFOAIuBlFQametYZc46A6QvY21yvIxQYRuFcTS6GBbANDCkxZOQtsnh6oLxQlzj71k7y5AXy0ZSALmVGUA2fPSnVTL0D5z00KUfzSBPzRkBtiZtIteqavVIVNheTylvftVK2wLIlxB5mxytKvVfBd37j5J8INuAu9RiTWCHtKaTmd8HbDM1H-sG-gfxMfoD
  priority: 102
  providerName: Scholars Portal
Title Epigenetic Mechanisms of Escape from BRAF Oncogene Dependency
URI https://www.proquest.com/docview/2547556050
https://www.proquest.com/docview/2301445652
https://pubmed.ncbi.nlm.nih.gov/PMC6826668
https://www.mdpi.com/2072-6694/11/10/1480/pdf?version=1570025965
UnpaywallVersion publishedVersion
Volume 11
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
journalDatabaseRights – providerCode: PRVAFT
  databaseName: Colorado Digital library
  customDbUrl:
  eissn: 2072-6694
  dateEnd: 99991231
  omitProxy: true
  ssIdentifier: ssj0000331767
  issn: 2072-6694
  databaseCode: KQ8
  dateStart: 20090101
  isFulltext: true
  titleUrlDefault: http://grweb.coalliance.org/oadl/oadl.html
  providerName: Colorado Alliance of Research Libraries
– providerCode: PRVEBS
  databaseName: EBSCOhost Academic Search Ultimate
  customDbUrl: https://search.ebscohost.com/login.aspx?authtype=ip,shib&custid=s3936755&profile=ehost&defaultdb=asn
  eissn: 2072-6694
  dateEnd: 99991231
  omitProxy: true
  ssIdentifier: ssj0000331767
  issn: 2072-6694
  databaseCode: ABDBF
  dateStart: 20100901
  isFulltext: true
  titleUrlDefault: https://search.ebscohost.com/direct.asp?db=asn
  providerName: EBSCOhost
– providerCode: PRVBFR
  databaseName: Free Medical Journals
  customDbUrl:
  eissn: 2072-6694
  dateEnd: 99991231
  omitProxy: true
  ssIdentifier: ssj0000331767
  issn: 2072-6694
  databaseCode: DIK
  dateStart: 20090101
  isFulltext: true
  titleUrlDefault: http://www.freemedicaljournals.com
  providerName: Flying Publisher
– providerCode: PRVFQY
  databaseName: GFMER Free Medical Journals
  customDbUrl:
  eissn: 2072-6694
  dateEnd: 99991231
  omitProxy: true
  ssIdentifier: ssj0000331767
  issn: 2072-6694
  databaseCode: GX1
  dateStart: 20090101
  isFulltext: true
  titleUrlDefault: http://www.gfmer.ch/Medical_journals/Free_medical.php
  providerName: Geneva Foundation for Medical Education and Research
– providerCode: PRVHPJ
  databaseName: ROAD: Directory of Open Access Scholarly Resources
  customDbUrl:
  eissn: 2072-6694
  dateEnd: 99991231
  omitProxy: true
  ssIdentifier: ssj0000331767
  issn: 2072-6694
  databaseCode: M~E
  dateStart: 20090101
  isFulltext: true
  titleUrlDefault: https://road.issn.org
  providerName: ISSN International Centre
– providerCode: PRVAQN
  databaseName: PubMed Central
  customDbUrl:
  eissn: 2072-6694
  dateEnd: 99991231
  omitProxy: true
  ssIdentifier: ssj0000331767
  issn: 2072-6694
  databaseCode: RPM
  dateStart: 20090101
  isFulltext: true
  titleUrlDefault: https://www.ncbi.nlm.nih.gov/pmc/
  providerName: National Library of Medicine
– providerCode: PRVPQU
  databaseName: ProQuest Central
  customDbUrl: http://www.proquest.com/pqcentral?accountid=15518
  eissn: 2072-6694
  dateEnd: 99991231
  omitProxy: true
  ssIdentifier: ssj0000331767
  issn: 2072-6694
  databaseCode: BENPR
  dateStart: 20090101
  isFulltext: true
  titleUrlDefault: https://www.proquest.com/central
  providerName: ProQuest
– providerCode: PRVFZP
  databaseName: Scholars Portal Journals: Open Access
  customDbUrl:
  eissn: 2072-6694
  dateEnd: 20250930
  omitProxy: true
  ssIdentifier: ssj0000331767
  issn: 2072-6694
  databaseCode: M48
  dateStart: 20091201
  isFulltext: true
  titleUrlDefault: http://journals.scholarsportal.info
  providerName: Scholars Portal
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1db9MwFL1irQS88D1RGJWReICHtE5iO8nDNHWjZUJqmSYqlafIn6KipNXSgsav57pJu7USQoiXKJJt2Y5943Ps63MB3sQqZCaNTKCkiwOmjQuUTpG4GppolsXWrcV0hiNxPmYfJ3xy6xa_d6tEKj5d_6QjmkSBEBnrhiGadxehO-0ujDv5Ue8lhV6dHQG84AfQFBz5cwOa49FF74uPKbcpXSn6xMjuu9p_yqsSDdzvpNHdxegGYe77R95bFQt5_VPOZrcWn8FDkJtmVz4n3zqrperoX3uKjv_Tr0fwoEampFdNpcdwxxZP4O6wPnt_Csf9hVfu9JceydD6C8PT8ntJ5o70S-9FRfxNFXJ62RuQT4We-6zkfR1iV18_g_Gg__nsPKiDLwSaCbYMMsUl5U7G3IWpDi2-sizJTEaVU_hQLtPaIrvUiIEsFTJJYocdMQjgKJM2PoRGMS_scyDCUBdJI5D9YEqcqCSVYcaNNgrJIqct6GxGIde1MrkPkDHLkaH4Ycv3hq0Fb7cFFpUox5-zHm2GNa-ts8yRFCccoZ6v-vU2Ge3KH5bIws5XmGfNNRHuRi1IdqbDtkqvzL2bUky_rhW6BZI2IdIWvNtOnL819MU_5H0J9xG3ZZVP4RE0llcr-wqx0VK1oXnaH11ctuHgwyTE55Cl7dokfgPdhA49
linkProvider Unpaywall
linkToHtml http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV1Lb9NAEB6VVKJcEE9hKO0igQQH043Xrz1EVR-JUtoEVLVSb-4-RaVghzpRlT_Hb2PWsV1SCTj1Ylna9UMzuzvz7c58A_CeyW6o00D7Uljmh0pbX6oUgaumiQo5M7Yi0xmN4-F5-OUiuliDX00ujAurbNbEaqHWhXJ75DsIZJIIzXNEd6c_fVc1yp2uNiU0RF1aQfcqirE6sePYLG4QwpW9o0PU94cgGPTPDoZ-XWXAV2EcznwuI0EjK1hku6nqGrwNecI1p9JKvEjLlTIIoxQae0NjkSTMIojQ6KnQUBiG730A6-h2BGEH1vf742-n7S4PZWif42TJKcQYpzvKKfO6xCXG7eXRVXN46-PejdDcmOdTsbgRk8kf5m_wBB7XfivZWw60p7Bm8mfwcFSfzD-HXn_qeD1dSiQZGZdOfFX-KElhSb90MVbE5bGQ_dO9Afmaq8J1JYd1AV61eAHn9yK0l9DJi9y8AhJragOhY8RG2MISmaSiyyOttEQoGVEPPjcSylTNW-7KZ0wyxC9OpNkdkXrwsX1guqTs-HvXzUbkWT13y-x2pHnwrm3GWeeOUkRuijn2qZAoOsOBB8mKqtpPOt7u1Zb86nvF3x0jpIvj1INPrVL_96Ov__2j27AxPBudZCdH4-M38AidOr4MONyEzux6bt6i4zSTW_XoJHB53xPiNz3TLuA
linkToPdf http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV3db9MwED-NThq8ID5FYICRQIKHUDdO4uShQhtttTFapolJewv-FJNKUpZWU_9F_irOqdPRScDTXqJIdj50Z_vuZ9_9DuA1k71YZ5EOpbAsjJW2oVQZAldNuYpzZmxDpjOepAen8aez5GwLfrW5MC6ssl0Tm4VaV8rtkXcRyPAEzXNCu9aHRRwPRh9mP0NXQcqdtLblNIQvs6D7Dd2YT_I4MstLhHN1_3CAun8TRaPh148Hoa84EKo4jedhLhNBEytYYnuZ6hm8jXOe65xKK_Eiba6UQUil0PAbmgrOmUVAodFrobEwDN97C7Y5yzPage394eT4ZL3jQxna6pSv-IUYy2lXOcVe1LjcuH09umkar_zd69GatxflTCwvxXT6hykc3YO73ocle6tBdx-2TPkAdsb-lP4h9Iczx_Hp0iPJ2LjU4vP6R00qS4a1i7ciLqeF7J_sjciXUlWuKxn4Yrxq-QhOb0Roj6FTVqV5AiTV1EZCp4iTsIVxyTPRyxOttERYmdAA3rcSKpTnMHelNKYFYhkn0uKaSAN4u35gtqLv-HvX3VbkhZ_HdXE16gJ4tW7GGeiOVURpqgX2aVApOsZRAHxDVetPOg7vzZby_HvD5Z0ivEvTLIB3a6X-70ef_vtHX8IOTozi8-Hk6BncQf8uX8Ue7kJnfrEwz9GHmssXfnAS-HbT8-E3HowzGg
linkToUnpaywall http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1bixMxFD5oF9SX9bpYXSWCD_owbWYml8mDSNWWRegqYmF9GnLFYp2WnXZl_fWedKZ1WxARX4aBJCSZnDP5vuTkC8Dz3KTMFZlLjA55wqwLibEFEldHpWUq92EtpjM-FScT9v6Mn105xR_DKpGKT9c_6YzKLBFCsX6aonv3EbrT_sKF1xftWlIa1dkRwAt-HQ4ER_7cgYPJ6cfBl3in3KZ0o-iTI7vv2_gpz2t08LiSRncno98Icz8-8uaqWujLH3o2uzL5jG6D3jS7iTn51lstTc_-3FN0_J9-3YHDFpmSQWNKd-Gar-7BjXG7934fXg0XUbkzHnokYx8PDE_r7zWZBzKsYxQViSdVyJtPgxH5UNl5zEretVfs2ssHMBkNP789SdrLFxLLBFsmynBNedA5D2lhU4-vTEnlFDXB4MMEZa1HdmkRA3kqtJR5wI44BHCUaZ8fQaeaV_4hEOFoyLQTyH4wJZdGFjpV3FlnkCxy2oXeZhRK2yqTxwsyZiUylDhs5d6wdeHFtsCiEeX4c9bjzbCWrXfWJZJiyRHqxaqfbZPRr-Jmia78fIV51lwT4W7WBbljDtsqozL3bko1_bpW6BZI2oQouvByazh_a-ijf8j7GG4hblNNTOExdJbnK_8EsdHSPG3N_xfoSgrY
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Epigenetic+Mechanisms+of+Escape+from+BRAF+Oncogene+Dependency&rft.jtitle=Cancers&rft.au=Khaliq%2C+Mehwish&rft.au=Fallahi-Sichani%2C+Mohammad&rft.date=2019-10-01&rft.issn=2072-6694&rft.eissn=2072-6694&rft.volume=11&rft.issue=10&rft_id=info:doi/10.3390%2Fcancers11101480&rft.externalDBID=NO_FULL_TEXT
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=2072-6694&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=2072-6694&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=2072-6694&client=summon