Genomic heterogeneity and efficacy of PI3K pathway inhibitors in patients with gynaecological cancer.
AKT
PI3K
mTOR inhibitors, gynecologic malignancies, mutant allele fraction
Journal
ESMO open
ISSN: 2059-7029
Titre abrégé: ESMO Open
Pays: England
ID NLM: 101690685
Informations de publication
Date de publication:
2019
2019
Historique:
received:
10
09
2018
revised:
23
11
2018
accepted:
24
11
2018
entrez:
10
4
2019
pubmed:
10
4
2019
medline:
10
4
2019
Statut:
epublish
Résumé
Aberrant PI3K/AKT/mTOR activation is common in gynaecological malignancies. However, predictive biomarkers of response to PI3K pathway inhibitors (PAMi) have yet to be identified. We analysed the outcomes of patients with advanced gynaecological cancer with available genomic data, treated with PAMi as single agents or in combination in phase I clinical trials. Clinical relevance of the A total of 50 patients with gynaecological cancer (24 ovarian; 15 endometrial; 11 cervical) with available targeted mutation profiling were selected. PAMi therapy was matched to Our study demonstrates that patients with advanced gynaecological cancer, refractory to standard therapies, achieved meaningful clinical benefit from PAMi. The impact of
Identifiants
pubmed: 30962959
doi: 10.1136/esmoopen-2018-000444
pii: S2059-7029(20)30169-1
pmc: PMC6435251
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e000444Déclaration de conflit d'intérêts
Competing interests: AO is a consultant/advisory board member of AstraZeneca, Clovis, Tesaro, Roche and PharmaMar. RD reports personal fees from Roche, outside the submitted work.
Références
Lancet Oncol. 2015 Oct;16(13):1324-34
pubmed: 26342236
Virchows Arch. 2017 Jan;470(1):21-27
pubmed: 27853865
Cancer. 2014 Feb 15;120(4):603-10
pubmed: 24166148
Cancer Res. 2009 Jan 1;69(1):143-50
pubmed: 19117997
N Engl J Med. 2013 Jun 20;368(25):2385-94
pubmed: 23724913
Nature. 2007 Jul 26;448(7152):439-44
pubmed: 17611497
Br J Cancer. 2013 May 14;108(9):1771-7
pubmed: 23612453
J Clin Oncol. 2016 Mar 10;34(8):871-8
pubmed: 26811525
Cancer Lett. 2008 Mar 8;261(1):120-6
pubmed: 18180098
Cancer. 2010 Dec 1;116(23):5415-9
pubmed: 20681032
Int J Cancer. 2020 Jul 15;147(2):413-422
pubmed: 31714586
J Clin Oncol. 2011 Aug 20;29(24):3278-85
pubmed: 21788564
Cancer. 2013 Nov 1;119(21):3776-83
pubmed: 24037752
Oncologist. 2014 Jun;19(6):616-22
pubmed: 24797823
J Natl Compr Canc Netw. 2016 Sep;14(9):1165-73
pubmed: 27587626
Ann Oncol. 2014 Oct;25(10):1948-1953
pubmed: 25009007
Nature. 2011 Jun 29;474(7353):609-15
pubmed: 21720365
Sci Transl Med. 2015 Apr 15;7(283):283ra54
pubmed: 25877892
Gynecol Oncol. 2013 Apr;129(1):22-7
pubmed: 23262204
J Clin Oncol. 2010 Feb 20;28(6):1075-83
pubmed: 20085938
Breast Cancer Res Treat. 2014 Oct;147(3):579-88
pubmed: 25209003
Gynecol Oncol. 2015 Feb;136(2):246-53
pubmed: 25528496
J Clin Oncol. 2010 Nov 20;28(33):4877-83
pubmed: 20921468
Nat Med. 2017 Jun;23(6):703-713
pubmed: 28481359
Clin Cancer Res. 2005 Apr 15;11(8):2875-8
pubmed: 15837735
Nature. 2017 Mar 16;543(7645):378-384
pubmed: 28112728
Oncotarget. 2015 Aug 21;6(24):20099-110
pubmed: 26015395
Clin Cancer Res. 2012 Nov 15;18(22):6373-83
pubmed: 22966018
J Clin Oncol. 2012 Mar 10;30(8):777-82
pubmed: 22271473
J Clin Invest. 2010 Aug;120(8):2858-66
pubmed: 20664172
Oncotarget. 2014 Sep 30;5(18):8544-57
pubmed: 25261369
Gynecol Oncol. 2014 Nov;135(2):184-9
pubmed: 25173583
Lancet. 2007 Jan 6;369(9555):29-36
pubmed: 17208639
Mol Cancer Ther. 2011 Mar;10(3):558-65
pubmed: 21216929
J Clin Oncol. 2017 Jul 10;35(20):2251-2259
pubmed: 28489509
Mol Oncol. 2017 Sep;11(9):1263-1272
pubmed: 28618197
Am J Pathol. 2009 May;174(5):1597-601
pubmed: 19349352
Cancer Res. 2013 Jan 1;73(1):276-84
pubmed: 23066039
J Clin Oncol. 2015 Sep 1;33(25):2753-62
pubmed: 26014291
Br J Cancer. 2013 Mar 19;108(5):1021-6
pubmed: 23403817
J Clin Oncol. 2015 Nov 1;33(31):3576-82
pubmed: 26077241
J Clin Oncol. 2015 Jan 20;33(3):244-50
pubmed: 25366685
Cancer. 2016 Nov 15;122(22):3519-3528
pubmed: 27603005
JCI Insight. 2016 Nov 17;1(19):e87062
pubmed: 27882345
Gynecol Oncol. 2016 Feb;140(2):333-44
pubmed: 26432040
Target Oncol. 2011 Mar;6(1):17-27
pubmed: 21547705
Mol Cancer Ther. 2016 May;15(5):1106-12
pubmed: 27037411
Nat Med. 2008 Dec;14(12):1351-6
pubmed: 19029981
Lancet Oncol. 2017 Jan;18(1):75-87
pubmed: 27908594
Cancer Res. 2006 Feb 1;66(3):1500-8
pubmed: 16452206
Clin Cancer Res. 2015 Mar 1;21(5):1087-97
pubmed: 25248381
Genome Med. 2016 Oct 25;8(1):109
pubmed: 27782854
Oncogene. 2008 Sep 18;27(41):5527-41
pubmed: 18794886
Sci Transl Med. 2015 Apr 15;7(283):283ra51
pubmed: 25877889
Oncotarget. 2014 Nov 30;5(22):11168-79
pubmed: 25426553
Cancer Discov. 2012 Nov;2(11):1036-47
pubmed: 22915752
Gynecol Oncol. 2010 Jun;117(3):473-6
pubmed: 20347480
Clin Cancer Res. 2006 Oct 15;12(20 Pt 1):5932-5
pubmed: 17062663
NPJ Precis Oncol. 2018 Sep 17;2:20
pubmed: 30246154
Gynecol Oncol. 2006 Apr;101(1):71-5
pubmed: 16290000
Int J Gynecol Cancer. 2014 May;24(4):713-7
pubmed: 24651628
Nature. 2013 May 2;497(7447):67-73
pubmed: 23636398
Gynecol Oncol. 2013 Aug;130(2):269-74
pubmed: 23672928
Gynecol Oncol. 2011 Oct;123(1):19-26
pubmed: 21752435
Gynecol Oncol. 2012 Jul;126(1):47-53
pubmed: 22487539
N Engl J Med. 2014 Nov 13;371(20):1877-88
pubmed: 25265492
Mol Cancer Ther. 2015 Jun;14(6):1488-94
pubmed: 25852059
Gynecol Oncol. 2014 Mar;132(3):585-92
pubmed: 24456823
J Clin Oncol. 2014 May 1;32(13):1317-23
pubmed: 24663044
J Clin Oncol. 2011 Aug 20;29(24):3316-21
pubmed: 21788562