BRAF mutant colorectal cancer: ErbB2 expression levels as predictive factor for the response to combined BRAF/ErbB inhibitors.
Afatinib
/ administration & dosage
Antineoplastic Combined Chemotherapy Protocols
/ pharmacology
Cell Line, Tumor
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
Colorectal Neoplasms
/ drug therapy
Humans
Molecular Targeted Therapy
/ methods
Mutation
Panitumumab
/ administration & dosage
Proto-Oncogene Proteins B-raf
/ antagonists & inhibitors
Receptor, ErbB-2
/ antagonists & inhibitors
Signal Transduction
/ drug effects
Vemurafenib
/ administration & dosage
Afatinib
BRAFV600E mutation
Colon cancer
ErbB2
Molecular therapy
Vemurafenib
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
17 Feb 2020
17 Feb 2020
Historique:
received:
10
09
2019
accepted:
29
01
2020
entrez:
19
2
2020
pubmed:
19
2
2020
medline:
24
11
2020
Statut:
epublish
Résumé
Colorectal cancer (CRC) is a heterogeneous disease with a complex biology and a wide number of altered genes such as BRAF, KRAS and PIK3CA. Advances with new-targeted therapies have been achieved and available treating options have prolonged patient's survival. However, BRAF-mutated CRC patients remain unresponsive to available therapies with RAF inhibitors (RAFi) alone or combined with ErbB inhibitors (ErbBi). These unmet needs require further exploitation of oncogenic signaling in order to set up individualized treatments. To this end, we tested the efficacy of single agent or combined treatments using the BRAFi, vemurafenib and two different ErbBi: panitumumab and afatinib in CRC cells characterized by different molecular phenotypes. Combination strategies with BRAFi and ErbBi achieved a better response in BRAF Our findings support the importance of ErbB2 evaluation in BRAF-mutated CRC patients and its role as a positive predictor factor of response to BRAFi/ErbBi combination.
Sections du résumé
BACKGROUND
BACKGROUND
Colorectal cancer (CRC) is a heterogeneous disease with a complex biology and a wide number of altered genes such as BRAF, KRAS and PIK3CA. Advances with new-targeted therapies have been achieved and available treating options have prolonged patient's survival. However, BRAF-mutated CRC patients remain unresponsive to available therapies with RAF inhibitors (RAFi) alone or combined with ErbB inhibitors (ErbBi). These unmet needs require further exploitation of oncogenic signaling in order to set up individualized treatments.
METHODS
METHODS
To this end, we tested the efficacy of single agent or combined treatments using the BRAFi, vemurafenib and two different ErbBi: panitumumab and afatinib in CRC cells characterized by different molecular phenotypes.
RESULTS
RESULTS
Combination strategies with BRAFi and ErbBi achieved a better response in BRAF
CONCLUSIONS
CONCLUSIONS
Our findings support the importance of ErbB2 evaluation in BRAF-mutated CRC patients and its role as a positive predictor factor of response to BRAFi/ErbBi combination.
Identifiants
pubmed: 32066410
doi: 10.1186/s12885-020-6586-0
pii: 10.1186/s12885-020-6586-0
pmc: PMC7027203
doi:
Substances chimiques
Vemurafenib
207SMY3FQT
Afatinib
41UD74L59M
Panitumumab
6A901E312A
ERBB2 protein, human
EC 2.7.10.1
Receptor, ErbB-2
EC 2.7.10.1
BRAF protein, human
EC 2.7.11.1
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
129Subventions
Organisme : Associazione Italiana per la Ricerca sul Cancro (IT)
ID : AIRC5x1000
Organisme : Istituto Italiano di Tecnologia
ID : IIT
Organisme : Sapienza Università di Roma
ID : Ateneo
Organisme : Ministero dell'Istruzione, dell'Università e della Ricerca
ID : PRIN
Organisme : Ministero dell'Istruzione, dell'Università e della Ricerca
ID : PON
Organisme : Ministero dell'Istruzione, dell'Università e della Ricerca
ID : FIRB
Organisme : Istituto Pasteur-Fondazione Cenci Bolognetti
ID : NA
Références
J Clin Oncol. 2008 Dec 10;26(35):5705-12
pubmed: 19001320
Lancet. 2019 Oct 19;394(10207):1467-1480
pubmed: 31631858
Expert Opin Ther Pat. 2017 May;27(5):527-538
pubmed: 28366103
N Engl J Med. 2019 Oct 24;381(17):1632-1643
pubmed: 31566309
Oncol Rep. 2015 Sep;34(3):1087-96
pubmed: 26151224
J Pharmacol Exp Ther. 2012 Nov;343(2):342-50
pubmed: 22888144
Clin Cancer Res. 2013 Feb 1;19(3):657-67
pubmed: 23251002
Ann Oncol. 2016 Aug;27(8):1456-66
pubmed: 27154421
J Clin Oncol. 2011 Jul 1;29(19):2675-82
pubmed: 21646616
J Clin Oncol. 2019 Jun 10;37(17):1460-1469
pubmed: 30892987
N Engl J Med. 2009 Jul 2;361(1):98-9
pubmed: 19571295
Cancer Discov. 2011 Nov;1(6):508-23
pubmed: 22586653
Lancet Oncol. 2010 Aug;11(8):753-62
pubmed: 20619739
Br J Cancer. 2011 Mar 1;104(5):856-62
pubmed: 21285991
Expert Opin Ther Targets. 2009 Mar;13(3):339-62
pubmed: 19236156
Clin Cancer Res. 2017 Jan 1;23(1):104-115
pubmed: 27354468
Eur J Cancer. 2015 Mar;51(5):587-94
pubmed: 25673558
Lancet. 2013 Jan 26;381(9863):303-12
pubmed: 23177514
Lancet Oncol. 2016 Jun;17(6):738-746
pubmed: 27108243
J Clin Oncol. 2009 Dec 10;27(35):5924-30
pubmed: 19884556
Cancer Biol Ther. 2014 Jul;15(7):826-31
pubmed: 24755613
J Clin Oncol. 2015 Dec 1;33(34):4032-8
pubmed: 26460303
Br J Clin Pharmacol. 2009 Oct;68(4):482-3
pubmed: 19843050
Curr Opin Investig Drugs. 2008 Dec;9(12):1336-46
pubmed: 19037840
J Clin Oncol. 2013 Sep 20;31(27):3327-34
pubmed: 23816960
N Engl J Med. 2011 Jun 30;364(26):2507-16
pubmed: 21639808
Clin Cancer Res. 2015 Mar 15;21(6):1313-20
pubmed: 25589621
Expert Opin Investig Drugs. 2019 Jan;28(1):29-38
pubmed: 30513002
J Clin Oncol. 2011 May 20;29(15):2011-9
pubmed: 21502544
PLoS One. 2014 May 30;9(5):e98528
pubmed: 24879338
Oncologist. 2019 Oct;24(10):1395-1402
pubmed: 30952821
J Clin Oncol. 2010 Jan 20;28(3):453-9
pubmed: 20008624
Nature. 2012 Jul 18;487(7407):330-7
pubmed: 22810696
J Clin Oncol. 2015 Dec 1;33(34):4023-31
pubmed: 26392102
Cancer Cell. 2012 Nov 13;22(5):668-82
pubmed: 23153539
Cancer Discov. 2012 Mar;2(3):227-35
pubmed: 22448344