دورية أكاديمية
أعرض في EDS

Functional diagnostics using fresh uncultured lung tumor cells to guide personalized treatments.

التفاصيل البيبلوغرافية
العنوان: Functional diagnostics using fresh uncultured lung tumor cells to guide personalized treatments.
المؤلفون: Talwelkar SS; Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki 00014, Finland., Mäyränpää MI; HUSLAB, Division of Pathology, Helsinki University Hospital and University of Helsinki, Helsinki 00029, Finland.; Department of Pathology, University of Helsinki, Helsinki 00014, Finland., Søraas L; Pontoppidans Gate 9B, 0462 Oslo, Norway., Potdar S; Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki 00014, Finland., Bao J; Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki 00014, Finland., Hemmes A; Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki 00014, Finland., Linnavirta N; Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki 00014, Finland., Lømo J; Department of Pathology, Oslo University Hospital, Oslo, Norway., Räsänen J; Department of Thoracic Surgery, Heart and Lung Center, Helsinki University Hospital, Helsinki, Finland., Knuuttila A; Department of Pulmonary Medicine, Heart and Lung Center, and Cancer Center, Helsinki University Hospital, Helsinki, Finland., Wennerberg K; Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki 00014, Finland.; BRIC-Biotech Research & Innovation Centre and Novo Nordisk Foundation Center for Stem Cell Biology (DanStem), University of Copenhagen, 2200 Copenhagen, Denmark., Verschuren EW; Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki 00014, Finland.
المصدر: Cell reports. Medicine [Cell Rep Med] 2021 Aug 17; Vol. 2 (8), pp. 100373. Date of Electronic Publication: 2021 Aug 17 (Print Publication: 2021).
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 101766894 Publication Model: eCollection Cited Medium: Internet ISSN: 2666-3791 (Electronic) Linking ISSN: 26663791 NLM ISO Abbreviation: Cell Rep Med
أسماء مطبوعة: Original Publication: [Cambridge, MA] : Cell Press, [2020]-
مواضيع طبية MeSH: Precision Medicine*, Lung Neoplasms/*diagnosis , Lung Neoplasms/*pathology, Adenocarcinoma of Lung/diagnosis ; Adenocarcinoma of Lung/pathology ; Adult ; Aged ; Animals ; Carcinoma, Non-Small-Cell Lung/diagnosis ; Carcinoma, Non-Small-Cell Lung/pathology ; Cellular Reprogramming ; Epithelial Cells/pathology ; Female ; Humans ; Male ; Mice ; Middle Aged ; Molecular Targeted Therapy ; Proto-Oncogene Proteins p21(ras)/genetics ; Signal Transduction ; Tumor Cells, Cultured
مستخلص: Functional profiling of a cancer patient's tumor cells holds potential to tailor personalized cancer treatment. Here, we report the utility of fresh uncultured tumor-derived EpCAM + epithelial cells (FUTCs) for ex vivo drug-response interrogation. Analysis of murine Kras mutant FUTCs demonstrates pharmacological and adaptive signaling profiles comparable to subtype-matched cultured cells. By applying FUTC profiling on non-small-cell lung cancer patient samples, we report robust drug-response data in 19 of 20 cases, with cells exhibiting targeted drug sensitivities corresponding to their oncogenic drivers. In one of these cases, an EGFR mutant lung adenocarcinoma patient refractory to osimertinib, FUTC profiling is used to guide compassionate treatment. FUTC profiling identifies selective sensitivity to disulfiram and the combination of carboplatin plus etoposide, and the patient receives substantial clinical benefit from treatment with these agents. We conclude that FUTC profiling provides a robust, rapid, and actionable assessment of personalized cancer treatment options.
Competing Interests: The authors declare no competing interests.
(© 2021 The Author(s).)
References: Hum Pathol. 2000 Apr;31(4):482-7. (PMID: 10821496)
Ann Oncol. 2019 May 1;30(5):661-663. (PMID: 30865225)
Nat Rev Cancer. 2015 Dec;15(12):747-56. (PMID: 26536825)
Oncotarget. 2015 Nov 17;6(36):38789-803. (PMID: 26515464)
J Clin Oncol. 2019 Feb 1;37(4):278-285. (PMID: 30550363)
Cancer Res. 2019 Apr 1;79(7):1658-1670. (PMID: 30737231)
N Engl J Med. 2012 Sep 27;367(13):1220-7. (PMID: 23013073)
N Engl J Med. 2018 Jan 11;378(2):113-125. (PMID: 29151359)
Cancer Cell. 2013 Jan 14;23(1):121-8. (PMID: 23245996)
Cancer Discov. 2016 Jul;6(7):754-69. (PMID: 27154822)
Am J Pathol. 2012 Feb;180(2):599-607. (PMID: 22189618)
Lancet Oncol. 2014 Apr;15(4):406-14. (PMID: 24636208)
Sci Rep. 2019 Nov 26;9(1):17613. (PMID: 31772293)
Sci Transl Med. 2018 Jun 20;10(446):. (PMID: 29925636)
Cancer Res. 2013 Jan 1;73(1):285-96. (PMID: 23087056)
Nature. 2019 Oct;574(7776):127-131. (PMID: 31570881)
Cancer Discov. 2013 Dec;3(12):1416-29. (PMID: 24056683)
J Thorac Oncol. 2019 Oct;14(10):1784-1793. (PMID: 31228622)
Nat Cancer. 2020 May;1(5):482-492. (PMID: 35121986)
Nat Genet. 2018 Oct;50(10):1399-1411. (PMID: 30262818)
Cell Rep. 2020 May 5;31(5):107588. (PMID: 32375033)
Oncotarget. 2017 Nov 6;8(62):105479-105491. (PMID: 29285266)
Cell Rep. 2017 Jan 17;18(3):673-684. (PMID: 28099846)
World J Surg Oncol. 2012 Apr 06;10:53. (PMID: 22482828)
Cancer Commun (Lond). 2019 Oct 1;39(1):53. (PMID: 31570104)
Nat Commun. 2018 Apr 19;9(1):1567. (PMID: 29674644)
J Thorac Oncol. 2012 Feb;7(2):306-15. (PMID: 22173704)
Clin Cancer Res. 2020 Mar 1;26(5):1162-1174. (PMID: 31694835)
Nature. 2016 Mar 3;531(7592):110-3. (PMID: 26909577)
Mol Oncol. 2013 Dec;7(6):1093-102. (PMID: 23993685)
Nat Rev Clin Oncol. 2012 Apr 17;9(6):338-50. (PMID: 22508028)
Sci Rep. 2015 Dec 09;5:17187. (PMID: 26647838)
Proc Natl Acad Sci U S A. 2015 Jul 21;112(29):9088-93. (PMID: 26150517)
Hum Pathol. 2004 Jan;35(1):122-8. (PMID: 14745734)
Sci Rep. 2017 Dec 12;7(1):17359. (PMID: 29234119)
J Clin Oncol. 2011 Aug 20;29(24):3328-30. (PMID: 21788567)
J Clin Oncol. 2004 Sep 1;22(17):3631-8. (PMID: 15289488)
Elife. 2017 Feb 01;6:. (PMID: 28145866)
J Pathol. 2018 May;245(1):101-113. (PMID: 29443392)
Bioinformatics. 2020 Jun 1;36(11):3602-3604. (PMID: 32119072)
Sci Signal. 2020 Jun 16;13(636):. (PMID: 32546544)
Nucleic Acids Res. 2013 Jan;41(Database issue):D955-61. (PMID: 23180760)
Science. 2014 Dec 19;346(6216):1480-6. (PMID: 25394791)
Cell Rep. 2017 Dec 12;21(11):3298-3309. (PMID: 29241554)
Int J Cancer. 2018 Jul 1;143(1):88-99. (PMID: 29341112)
J Thorac Dis. 2013 Oct;5 Suppl 5:S565-78. (PMID: 24163749)
EBioMedicine. 2018 Oct;36:196-208. (PMID: 30268834)
J Thorac Oncol. 2019 Sep;14(9):1556-1566. (PMID: 31108249)
Cancer Discov. 2015 Aug;5(8):860-77. (PMID: 26069186)
Cancer Discov. 2017 May;7(5):462-477. (PMID: 28331002)
Mol Cancer Ther. 2019 Oct;18(10):1863-1874. (PMID: 31320402)
Nat Commun. 2015 Mar 11;6:6377. (PMID: 25758528)
Lancet Haematol. 2017 Dec;4(12):e595-e606. (PMID: 29153976)
Medicine (Baltimore). 2018 May;97(18):e0650. (PMID: 29718881)
Sci Rep. 2014 Jun 05;4:5193. (PMID: 24898935)
Anticancer Res. 2009 May;29(5):1817-22. (PMID: 19443410)
Oncotarget. 2017 Feb 14;8(7):11114-11126. (PMID: 28052041)
Nat Commun. 2019 Sep 5;10(1):3991. (PMID: 31488816)
فهرسة مساهمة: Keywords: ALK; EGFR; KRAS; drug sensitivity and resistance testing; ex vivo drug screening; functional diagnostics; lung cancer; personalized medicine; pharmacogenomics; targeted therapy
المشرفين على المادة: 0 (KRAS protein, human)
EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
تواريخ الأحداث: Date Created: 20210901 Date Completed: 20220303 Latest Revision: 20240403
رمز التحديث: 20240403
مُعرف محوري في PubMed: PMC8385325
DOI: 10.1016/j.xcrm.2021.100373
PMID: 34467250
قاعدة البيانات: MEDLINE
الوصف
تدمد:2666-3791
DOI:10.1016/j.xcrm.2021.100373