The drug efficacy testing in 3D cultures platform identifies effective drugs for ovarian cancer patients.
Journal
NPJ precision oncology
ISSN: 2397-768X
Titre abrégé: NPJ Precis Oncol
Pays: England
ID NLM: 101708166
Informations de publication
Date de publication:
31 Oct 2023
31 Oct 2023
Historique:
received:
27
03
2023
accepted:
06
10
2023
medline:
1
11
2023
pubmed:
1
11
2023
entrez:
1
11
2023
Statut:
epublish
Résumé
Most patients with advanced ovarian cancer (OC) relapse and progress despite systemic therapy, pointing to the need for improved and tailored therapy options. Functional precision medicine can help to identify effective therapies for individual patients in a clinically relevant timeframe. Here, we present a scalable functional precision medicine platform: DET3Ct (Drug Efficacy Testing in 3D Cultures), where the response of patient cells to drugs and drug combinations are quantified with live-cell imaging. We demonstrate the delivery of individual drug sensitivity profiles in 20 samples from 16 patients with ovarian cancer in both 2D and 3D culture formats, achieving over 90% success rate in providing results six days after operation. In this cohort all patients received carboplatin. The carboplatin sensitivity scores were significantly different for patients with a progression free interval (PFI) less than or equal to 12 months and those with more than 12 months (p < 0.05). We find that the 3D culture format better retains proliferation and characteristics of the in vivo setting. Using the DET3Ct platform we evaluate 27 tailored combinations with results available 10 days after operation. Notably, carboplatin and A-1331852 (Bcl-xL inhibitor) showed an additive effect in four of eight OC samples tested, while afatinib and A-1331852 led to synergy in five of seven OC models. In conclusion, our 3D DET3Ct platform can rapidly define potential, clinically relevant data on efficacy of existing drugs in OC for precision medicine purposes, as well as provide insights on emerging drugs and drug combinations that warrant testing in clinical trials.
Identifiants
pubmed: 37907613
doi: 10.1038/s41698-023-00463-z
pii: 10.1038/s41698-023-00463-z
pmc: PMC10618545
doi:
Types de publication
Journal Article
Langues
eng
Pagination
111Subventions
Organisme : Vetenskapsrådet (Swedish Research Council)
ID : 2021-03420
Organisme : Vetenskapsrådet (Swedish Research Council)
ID : 2017-06095
Organisme : Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation)
ID : 2015.0291
Informations de copyright
© 2023. The Author(s).
Références
Springerplus. 2016 Jul 28;5(1):1197
pubmed: 27516935
Arch Med Sci. 2018 Jun;14(4):910-919
pubmed: 30002710
Nat Commun. 2017 Aug 28;8(1):365
pubmed: 28848242
Cancer Treat Res Commun. 2021;29:100463
pubmed: 34601320
Oncotarget. 2017 Jul 4;8(27):44295-44311
pubmed: 28574828
Cancer Discov. 2022 Feb;12(2):372-387
pubmed: 34635570
Mol Cancer Ther. 2019 Mar;18(3):642-655
pubmed: 30679390
Science. 2014 Dec 19;346(6216):1480-6
pubmed: 25394791
Cell Rep. 2017 Dec 12;21(11):3298-3309
pubmed: 29241554
Aging (Albany NY). 2021 Aug 5;13(15):19750-19759
pubmed: 34351305
Clin Cancer Res. 2022 Jan 1;28(1):36-44
pubmed: 34645648
Nat Rev Cancer. 2015 Dec;15(12):747-56
pubmed: 26536825
Eur J Cancer. 2000 Oct;36(16):2120-7
pubmed: 11044651
Eur J Cancer. 2018 Jan;88:31-37
pubmed: 29179135
Cancer Metab. 2022 May 16;10(1):9
pubmed: 35578327
Oncol Rep. 2015 Apr;33(4):1837-43
pubmed: 25634491
Int J Mol Sci. 2018 Dec 08;19(12):
pubmed: 30544835
Int J Mol Sci. 2020 Dec 30;22(1):
pubmed: 33396714
Cancer Discov. 2022 Feb;12(2):388-401
pubmed: 34789538
Nat Commun. 2020 Feb 13;11(1):822
pubmed: 32054838
Int J Mol Sci. 2016 Dec 15;17(12):
pubmed: 27983698
Gynecol Oncol. 2005 Feb;96(2):287-95
pubmed: 15661210
J Cell Sci. 2017 Jan 1;130(1):203-218
pubmed: 27663511
Cancer Cell. 2019 Jul 8;36(1):84-99.e8
pubmed: 31287994
Int J Cancer. 2010 Feb 15;126(4):885-95
pubmed: 19634140
Sci Rep. 2017 Sep 4;7(1):10382
pubmed: 28871147
Front Med (Lausanne). 2022 Jul 08;9:912641
pubmed: 35879922
Lancet. 2021 Jan 23;397(10271):281-292
pubmed: 33485453
Nucleic Acids Res. 2022 Jul 5;50(W1):W739-W743
pubmed: 35580060
Mol Syst Biol. 2017 Nov 27;13(11):955
pubmed: 29180611
Cancer Cell. 2022 Jan 10;40(1):26-35
pubmed: 34951956
Bioinformatics. 2020 Jun 1;36(11):3602-3604
pubmed: 32119072
Mol Med Rep. 2021 Jan;23(1):
pubmed: 33200796
Cancers (Basel). 2020 May 23;12(5):
pubmed: 32456205
Gynecol Oncol. 1990 Feb;36(2):207-11
pubmed: 2404837
J Clin Oncol. 1991 Mar;9(3):389-93
pubmed: 1999708
Cancer Sci. 2021 Feb;112(2):918-931
pubmed: 33244783
Sci Transl Med. 2022 Oct 19;14(667):eabn7824
pubmed: 36260690
Cancer Discov. 2017 May;7(5):462-477
pubmed: 28331002
Nat Med. 2019 Dec;25(12):1938-1947
pubmed: 31792461
Cancer Cell. 2021 Mar 8;39(3):288-293
pubmed: 33482122
Nat Rev Mol Cell Biol. 2020 Oct;21(10):607-632
pubmed: 32576977
Oncogene. 2009 Feb 26;28(8):1151-61
pubmed: 19137016
Lab Invest. 2013 May;93(5):528-42
pubmed: 23459371
Nat Med. 2017 Sep 8;23(9):1028-1035
pubmed: 28886003
Cancer Treat Res Commun. 2022;33:100629
pubmed: 36127285
Int J Cancer. 2010 Jul 1;127(1):1-8
pubmed: 20143388
Biomaterials. 2010 Nov;31(32):8494-506
pubmed: 20709389
PLoS Med. 2007 Oct;4(10):1669-79; discussion 1680
pubmed: 17973572
Am J Pathol. 2007 Mar;170(3):1054-63
pubmed: 17322388