دورية أكاديمية
أعرض في EDS

FEN1 Inhibition as a Potential Novel Targeted Therapy against Breast Cancer and the Prognostic Relevance of FEN1.

التفاصيل البيبلوغرافية
العنوان: FEN1 Inhibition as a Potential Novel Targeted Therapy against Breast Cancer and the Prognostic Relevance of FEN1.
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.
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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
الوصف
تدمد:1422-0067
DOI:10.3390/ijms25042110