دورية أكاديمية
FEN1 Inhibition as a Potential Novel Targeted Therapy against Breast Cancer and the Prognostic Relevance of FEN1.
العنوان: | FEN1 Inhibition as a Potential Novel Targeted Therapy against Breast Cancer and the Prognostic Relevance of FEN1. |
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المؤلفون: | Berfelde J; Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany., Hildebrand LS; Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.; Comprehensive Cancer Center Erlangen-Europäische Metropolregion Nürnberg (CCC ER-EMN), 91054 Erlangen, Germany., Kuhlmann L; Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.; Comprehensive Cancer Center Erlangen-Europäische Metropolregion Nürnberg (CCC ER-EMN), 91054 Erlangen, Germany., Fietkau R; Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.; Comprehensive Cancer Center Erlangen-Europäische Metropolregion Nürnberg (CCC ER-EMN), 91054 Erlangen, Germany., Distel LV; Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.; Comprehensive Cancer Center Erlangen-Europäische Metropolregion Nürnberg (CCC ER-EMN), 91054 Erlangen, Germany. |
المصدر: | International journal of molecular sciences [Int J Mol Sci] 2024 Feb 09; Vol. 25 (4). Date of Electronic Publication: 2024 Feb 09. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Basel, Switzerland : MDPI, [2000- |
مواضيع طبية MeSH: | Antineoplastic Agents*/pharmacology , Breast Neoplasms*/drug therapy , Breast Neoplasms*/genetics , Breast Neoplasms*/pathology , Flap Endonucleases*/genetics , Flap Endonucleases*/metabolism, Female ; Humans ; DNA Repair ; Prognosis |
مستخلص: | To improve breast cancer treatment and to enable new strategies for therapeutic resistance, therapeutic targets are constantly being studied. Potential targets are proteins of DNA repair and replication and genomic integrity, such as Flap Endonuclease 1 (FEN1). This study investigated the effects of FEN1 inhibitor FEN1-IN-4 in combination with ionizing radiation on cell death, clonogenic survival, the cell cycle, senescence, doubling time, DNA double-strand breaks and micronuclei in breast cancer cells, breast cells and healthy skin fibroblasts. Furthermore, the variation in the baseline FEN1 level and its influence on treatment prognosis was investigated. The cell lines show specific response patterns in the aspects studied and have heterogeneous baseline FEN1 levels. FEN1-IN-4 has cytotoxic, cytostatic and radiosensitizing effects, expressed through increasing cell death by apoptosis and necrosis, G2M share, senescence, double-strand breaks and a reduced survival fraction. Nevertheless, some cells are less affected by the cytotoxicity and fibroblasts show a rather limited response. In vivo, high FEN1 mRNA expression worsens the prognosis of breast cancer patients. Due to the increased expression in breast cancer tissue, FEN1 could represent a new tumor and prognosis marker and FEN1-IN-4 may serve as a new potent agent in personalized medicine and targeted breast cancer therapy. |
References: | Nat Protoc. 2009;4(12):1798-806. (PMID: 20010931) Breast. 2022 Dec;66:15-23. (PMID: 36084384) Int J Mol Med. 2014 May;33(5):1268-74. (PMID: 24590400) BMC Genomics. 2016 Aug 22;17 Suppl 7:525. (PMID: 27556158) Nucleic Acids Res. 2011 Feb;39(3):781-94. (PMID: 20929870) EMBO Rep. 2005 Jan;6(1):83-9. (PMID: 15592449) Ann Transl Med. 2021 Feb;9(3):258. (PMID: 33708885) Cancer Med. 2019 Dec;8(18):7774-7780. (PMID: 31670906) EMBO J. 1994 Mar 1;13(5):1235-46. (PMID: 8131753) Nucleic Acids Res. 2018 Jun 20;46(11):5634-5650. (PMID: 29741650) Mutat Res. 2000 Nov 20;455(1-2):81-95. (PMID: 11113469) Sci Rep. 2019 Feb 14;9(1):2074. (PMID: 30765770) Annu Rev Biochem. 2013;82:119-38. (PMID: 23451868) Lancet Oncol. 2001 Jun;2(6):366-70. (PMID: 11905753) Int J Biol Sci. 2022 Jan 1;18(3):1022-1038. (PMID: 35173534) Geroscience. 2023 Jun;45(3):1889-1898. (PMID: 36856946) Proc Natl Acad Sci U S A. 2020 Aug 11;117(32):19415-19424. (PMID: 32719125) Nat Med. 2007 Jul;13(7):812-9. (PMID: 17589521) Clin Breast Cancer. 2018 Oct;18(5):e841-e850. (PMID: 30146351) BMC Cancer. 2015 Feb 13;15:50. (PMID: 25885449) J Cancer. 2017 Sep 12;8(16):3131-3141. (PMID: 29158785) Nature. 2000 Aug 17;406(6797):747-52. (PMID: 10963602) Breast Cancer Res. 2010;12(5):R68. (PMID: 20813035) Int J Mol Sci. 2024 Jan 24;25(3):. (PMID: 38338684) Int J Mol Sci. 2021 Mar 05;22(5):. (PMID: 33807717) Bioorg Med Chem Lett. 2005 Jan 17;15(2):277-81. (PMID: 15603939) Analyst. 2023 Jan 16;148(2):316-327. (PMID: 36484412) Bull Math Biol. 2012 Oct;74(10):2510-34. (PMID: 22914970) Nature. 2017 Aug 24;548(7668):461-465. (PMID: 28738408) Biochemistry. 1996 Sep 10;35(36):11668-76. (PMID: 8794747) Free Radic Biol Med. 2021 Feb 20;164:34-43. (PMID: 33418109) Molecules. 2023 Nov 09;28(22):. (PMID: 38005235) Dig Liver Dis. 2023 Aug 28;:. (PMID: 37648642) Cell Mol Life Sci. 2009 Mar;66(6):981-93. (PMID: 19153658) AJR Am J Roentgenol. 2018 Sep;211(3):470-484. (PMID: 29995496) J Biol Chem. 1996 Jul 5;271(27):16000-7. (PMID: 8663274) PLoS One. 2013 May 13;8(5):e62340. (PMID: 23675412) Front Pharmacol. 2021 Jan 15;11:601468. (PMID: 33628174) J Biol Chem. 2001 Feb 16;276(7):4901-8. (PMID: 11053418) Nat Protoc. 2006;1(5):2315-9. (PMID: 17406473) Cancers (Basel). 2020 Apr 23;12(4):. (PMID: 32340362) Front Genet. 2018 Oct 01;9:421. (PMID: 30337938) Oncol Rep. 2020 Dec;44(6):2443-2454. (PMID: 33125141) Adv Space Res. 2009;43(8):1171-1178. (PMID: 20046946) Strahlenther Onkol. 2023 Dec;199(12):1091-1109. (PMID: 37041372) Mol Cell Biol. 2008 Jul;28(13):4310-9. (PMID: 18443037) Mol Oncol. 2014 Oct;8(7):1326-38. (PMID: 24880630) Cell Cycle. 2007 Jul 15;6(14):1682-6. (PMID: 17637566) Mol Cell Biol. 2005 Aug;25(16):6948-55. (PMID: 16055708) Radiat Oncol. 2012 Dec 05;7:206. (PMID: 23216894) Arch Toxicol. 2016 Nov;90(11):2657-2667. (PMID: 27542123) Radiat Oncol. 2015 Nov 04;10:223. (PMID: 26537797) Radiat Res. 1968 Mar;33(3):620-43. (PMID: 4867897) Cancer Res. 2006 Jan 1;66(1):41-5. (PMID: 16397213) Cell Cycle. 2016 Nov 16;15(22):3131-3145. (PMID: 27636097) Mol Cell. 2019 Mar 7;73(5):885-899.e6. (PMID: 30686591) Mol Oncol. 2017 Jun;11(6):640-654. (PMID: 28371273) Mol Cancer Res. 2008 Nov;6(11):1710-7. (PMID: 19010819) World J Clin Oncol. 2014 Aug 10;5(3):412-24. (PMID: 25114856) BMC Complement Altern Med. 2019 May 31;19(1):112. (PMID: 31151442) Biomolecules. 2023 Aug 01;13(8):. (PMID: 37627272) Mutagenesis. 2011 Jan;26(1):93-100. (PMID: 21164188) Am J Pathol. 2001 Jan;158(1):199-206. (PMID: 11141493) Cancer Cell. 2006 Dec;10(6):515-27. (PMID: 17157791) Geburtshilfe Frauenheilkd. 2013 Sep;73(9):932-940. (PMID: 24771945) Lancet. 2017 Mar 18;389(10074):1134-1150. (PMID: 27865536) Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5057-62. (PMID: 12679524) Mutagenesis. 2011 Jan;26(1):125-32. (PMID: 21164193) Comput Struct Biotechnol J. 2021 Jul 18;19:4101-4109. (PMID: 34527184) Front Cell Dev Biol. 2021 Jul 12;9:701073. (PMID: 34322487) Genes Dev. 1994 Jun 1;8(11):1344-55. (PMID: 7926735) J Pathol. 2010 Jan;220(2):263-80. (PMID: 19927298) Front Genet. 2013 Jul 11;4:131. (PMID: 23874352) Cells. 2023 Aug 22;12(17):. (PMID: 37681855) J Cancer. 2019 Oct 21;10(26):6618-6634. (PMID: 31777591) Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1303-8. (PMID: 9990019) Cancer Discov. 2022 Jan;12(1):31-46. (PMID: 35022204) Front Oncol. 2021 Oct 13;11:740002. (PMID: 34722291) Cell Death Discov. 2018 Feb 14;4:24. (PMID: 29531821) Biochem J. 1997 Jul 1;325 ( Pt 1):1-16. (PMID: 9224623) Mol Oncol. 2011 Feb;5(1):5-23. (PMID: 21147047) Br J Cancer. 2012 Feb 14;106(4):780-90. (PMID: 22187037) Mutagenesis. 2012 May;27(3):323-7. (PMID: 22086909) J Biol Chem. 2002 Nov 1;277(44):41715-24. (PMID: 12200445) J Vis Exp. 2013 Aug 02;(78):. (PMID: 23963434) Nucleic Acids Res. 2008 Oct;36(17):5678-94. (PMID: 18772227) Strahlenther Onkol. 2023 Dec;199(12):1080-1090. (PMID: 37620671) |
فهرسة مساهمة: | Keywords: FEN1; FEN1 inhibition; FEN1-IN-4; TNBC; apoptosis; breast cancer cell lines; ionizing radiation; necrosis; radiosensitivity; targeted therapy |
المشرفين على المادة: | 0 (Antineoplastic Agents) EC 3.1.11.- (FEN1 protein, human) EC 3.1.- (Flap Endonucleases) |
تواريخ الأحداث: | Date Created: 20240224 Date Completed: 20240226 Latest Revision: 20240313 |
رمز التحديث: | 20240313 |
مُعرف محوري في PubMed: | PMC10889347 |
DOI: | 10.3390/ijms25042110 |
PMID: | 38396787 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1422-0067 |
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DOI: | 10.3390/ijms25042110 |