Facilitating Drug Discovery in Breast Cancer by Virtually Screening Patients Using In Vitro Drug Response Modeling.
Wee1
breast cancer
drug discovery
drug imputation
transcriptome
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
20 Feb 2021
20 Feb 2021
Historique:
received:
19
01
2021
revised:
06
02
2021
accepted:
13
02
2021
entrez:
6
3
2021
pubmed:
7
3
2021
medline:
7
3
2021
Statut:
epublish
Résumé
(1) Background: Drug imputation methods often aim to translate in vitro drug response to in vivo drug efficacy predictions. While commonly used in retrospective analyses, our aim is to investigate the use of drug prediction methods for the generation of novel drug discovery hypotheses. Triple-negative breast cancer (TNBC) is a severe clinical challenge in need of new therapies. (2) Methods: We used an established machine learning approach to build models of drug response based on cell line transcriptome data, which we then applied to patient tumor data to obtain predicted sensitivity scores for hundreds of drugs in over 1000 breast cancer patients. We then examined the relationships between predicted drug response and patient clinical features. (3) Results: Our analysis recapitulated several suspected vulnerabilities in TNBC and identified a number of compounds-of-interest. AZD-1775, a Wee1 inhibitor, was predicted to have preferential activity in TNBC (
Identifiants
pubmed: 33672646
pii: cancers13040885
doi: 10.3390/cancers13040885
pmc: PMC7924213
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : NCI NIH HHS
ID : R01 CA204856
Pays : United States
Organisme : NIH HHS
ID : R01CA204856
Pays : United States
Références
PLoS One. 2015 May 07;10(5):e0124780
pubmed: 25951608
BMC Cancer. 2014 Jun 13;14:430
pubmed: 24927813
Breast Cancer Res Treat. 2017 Jan;161(2):279-287
pubmed: 27888421
BMC Cancer. 2014 Aug 07;14:570
pubmed: 25104095
Nat Rev Drug Discov. 2019 Jan;18(1):41-58
pubmed: 30310233
Nat Cancer. 2020 Feb;1(2):235-248
pubmed: 32613204
N Engl J Med. 2010 Nov 11;363(20):1938-48
pubmed: 21067385
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Cell Rep. 2018 Jan 30;22(5):1185-1199
pubmed: 29386107
Cancer Biol Ther. 2010 Apr 1;9(7):514-22
pubmed: 20107315
Clin Cancer Res. 2018 Dec 15;24(24):6594-6610
pubmed: 30181387
Mol Cancer Res. 2019 May;17(5):1115-1128
pubmed: 30679201
Biostatistics. 2019 Apr 1;20(2):273-286
pubmed: 29394327
Nat Rev Drug Discov. 2004 Aug;3(8):673-83
pubmed: 15286734
Int J Radiat Oncol Biol Phys. 2016 Jun 1;95(2):782-90
pubmed: 26975930
Brief Bioinform. 2017 Sep 1;18(5):820-829
pubmed: 27444372
Cell. 2014 Aug 14;158(4):929-944
pubmed: 25109877
Nature. 2012 Mar 28;483(7391):603-7
pubmed: 22460905
Clin Cancer Res. 2020 Mar 15;26(6):1213-1219
pubmed: 31857431
Pharmacol Ther. 2019 Jul;199:30-57
pubmed: 30825473
Biostatistics. 2007 Jan;8(1):118-27
pubmed: 16632515
BMC Cancer. 2013 Jun 03;13:271
pubmed: 23731661
J Cell Physiol. 2020 Jan;235(1):17-25
pubmed: 31206681
Mol Cancer Ther. 2009 Nov;8(11):2992-3000
pubmed: 19887545
Nature. 2012 Oct 4;490(7418):61-70
pubmed: 23000897
Cell Death Dis. 2016 Apr 14;7:e2195
pubmed: 27077811
Mol Med Rep. 2018 Feb;17(2):3344-3349
pubmed: 29257266
Clin Cancer Res. 2017 Aug 15;23(16):4540-4544
pubmed: 28442503
Pharmacol Ther. 2018 Nov;191:178-189
pubmed: 29953899
Mol Cancer. 2009 Jun 08;8:34
pubmed: 19500427
PLoS Comput Biol. 2020 Apr 20;16(4):e1007803
pubmed: 32310964
J Natl Cancer Inst. 2015 Aug 21;107(11):
pubmed: 26296641
Oncotarget. 2017 May 13;8(43):73705-73722
pubmed: 29088738
Br J Clin Pharmacol. 2013 Sep;76(3):358-69
pubmed: 23593991
Breast. 2014 Jun;23(3):250-8
pubmed: 24636978
J Clin Oncol. 2016 Dec 20;34(36):4354-4361
pubmed: 27998224
Lab Invest. 2019 Sep;99(9):1275-1286
pubmed: 30996295
Genome Res. 2017 Oct;27(10):1743-1751
pubmed: 28847918
Cell Syst. 2015 Dec 23;1(6):417-425
pubmed: 26771021
J Clin Invest. 2012 Apr;122(4):1541-52
pubmed: 22446188
Oncotarget. 2016 Aug 16;7(33):54067-54081
pubmed: 27322213
Nucleic Acids Res. 2013 Jan;41(Database issue):D955-61
pubmed: 23180760
J Clin Oncol. 2015 Oct 20;33(30):3409-15
pubmed: 25964244
Nucleic Acids Res. 2016 May 5;44(8):e71
pubmed: 26704973
Nat Genet. 2013 Oct;45(10):1113-20
pubmed: 24071849
Cancer Discov. 2015 Nov;5(11):1210-23
pubmed: 26482930
Clin Pharmacol Ther. 2013 Apr;93(4):335-41
pubmed: 23443757
Science. 1992 Sep 25;257(5078):1955-7
pubmed: 1384126
J Clin Oncol. 2016 Dec 20;34(36):4371-4380
pubmed: 27601554
Genome Biol. 2014 Mar 03;15(3):R47
pubmed: 24580837
Neoplasia. 2018 May;20(5):478-488
pubmed: 29605721
Cancer Discov. 2019 Mar;9(3):354-369
pubmed: 30518523
Clin Cancer Res. 2018 Jun 15;24(12):2740-2748
pubmed: 29535125
Cell Cycle. 2017;16(22):2176-2182
pubmed: 28296564
Clin Cancer Res. 2018 Aug 15;24(16):3820-3828
pubmed: 29798906
Oncologist. 2013;18(2):123-33
pubmed: 23404817