HIV-protease inhibitors potentiate the activity of carfilzomib in triple-negative breast cancer.

التفاصيل البيبلوغرافية
العنوان:	HIV-protease inhibitors potentiate the activity of carfilzomib in triple-negative breast cancer.
المؤلفون:	Besse A; Laboratory of Experimental Oncology, Department of Oncology and Hematology, Cantonal Hospital St. Gallen, St. Gallen, 9000, Switzerland.; Department of Biology, Faculty of Medicine, Masaryk University, Brno, 62500, Czech Republic., Sedlarikova L; Babak Myeloma Group, Department of Pathological Physiology, Masaryk University, Brno, 62500, Czech Republic.; Department of Biology, Faculty of Medicine, Masaryk University, Brno, 62500, Czech Republic., Buechler L; Laboratory of Experimental Oncology, Department of Oncology and Hematology, Cantonal Hospital St. Gallen, St. Gallen, 9000, Switzerland., Kraus M; Laboratory of Experimental Oncology, Department of Oncology and Hematology, Cantonal Hospital St. Gallen, St. Gallen, 9000, Switzerland., Yang CH; Department of Oncological Sciences, University of Utah, Salt Lake City, UT, USA.; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA., Strakova N; Department of Cytokinetics, Institute of Biophysics of the Czech Academy of Sciences, Brno, 612 00, Czech Republic.; Veterinary Research Institute, Brno, 62500, Czech Republic., Soucek K; Department of Cytokinetics, Institute of Biophysics of the Czech Academy of Sciences, Brno, 612 00, Czech Republic.; International Clinical Research Center, St. Anne's University Hospital Brno, Brno, Czech Republic., Navratil J; Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, 62500, Czech Republic.; Faculty of Medicine, Masaryk University, Brno, 62500, Czech Republic., Svoboda M; Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, 62500, Czech Republic.; Faculty of Medicine, Masaryk University, Brno, 62500, Czech Republic., Welm AL; Department of Oncological Sciences, University of Utah, Salt Lake City, UT, USA.; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA., Joerger M; Department of Oncology and Hematology, Cantonal Hospital St. Gallen, St. Gallen, 9000, Switzerland., Driessen C; Laboratory of Experimental Oncology, Department of Oncology and Hematology, Cantonal Hospital St. Gallen, St. Gallen, 9000, Switzerland.; Department of Oncology and Hematology, Cantonal Hospital St. Gallen, St. Gallen, 9000, Switzerland., Besse L; Laboratory of Experimental Oncology, Department of Oncology and Hematology, Cantonal Hospital St. Gallen, St. Gallen, 9000, Switzerland. Lenka.besse@kssg.ch.; Department of Biology, Faculty of Medicine, Masaryk University, Brno, 62500, Czech Republic. Lenka.besse@kssg.ch.
المصدر:	British journal of cancer [Br J Cancer] 2024 Jul 05. Date of Electronic Publication: 2024 Jul 05.
Publication Model:	Ahead of Print
نوع المنشور:	Journal Article
اللغة:	English
بيانات الدورية:	Publisher: Nature Publishing Group on behalf of Cancer Research UK Country of Publication: England NLM ID: 0370635 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-1827 (Electronic) Linking ISSN: 00070920 NLM ISO Abbreviation: Br J Cancer Subsets: MEDLINE
أسماء مطبوعة:	Publication: 2002- : London : Nature Publishing Group on behalf of Cancer Research UK Original Publication: London, Lewis.
مستخلص:	Background: Resistance to chemotherapy is a major problem in the treatment of patients with triple-negative breast cancer (TNBC). Preclinical data suggest that TNBC is dependent on proteasomes; however, clinical observations indicate that the efficacy of proteasome inhibitors in TNBC may be limited, suggesting the need for combination therapies. Methods: We compared bortezomib and carfilzomib and their combinations with nelfinavir and lopinavir in TNBC cell lines and primary cells with regard to their cytotoxic activity, functional proteasome inhibition, and induction of the unfolded protein response (UPR). Furthermore, we evaluated the involvement of sXBP1, ABCB1, and ABCG2 in the cytotoxic activity of drug combinations. Results: Carfilzomib, via proteasome β5 + β2 inhibition, is more cytotoxic in TNBC than bortezomib, which inhibits β5 + β1 proteasome subunits. The cytotoxicity of carfilzomib was significantly potentiated by nelfinavir or lopinavir. Carfilzomib with lopinavir induced endoplasmic reticulum stress and pro-apoptotic UPR through the accumulation of excess proteasomal substrate protein in TNBC in vitro. Moreover, lopinavir increased the intracellular availability of carfilzomib by inhibiting carfilzomib export from cells that express high levels and activity of ABCB1, but not ABCG2. Conclusion: Proteasome inhibition by carfilzomib combined with nelfinavir/lopinavir represents a potential treatment option for TNBC, warranting further investigation. (© 2024. The Author(s).)
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معلومات مُعتمدة:	KFS-4990-02-2020 Krebsliga Schweiz (Ligue Suisse Contre le Cancer); KFS-4990-02-2020 Krebsliga Schweiz (Ligue Suisse Contre le Cancer); U54CA224076 U.S. Department of Health & Human Services \| NIH \| National Cancer Institute (NCI); U54CA224076 U.S. Department of Health & Human Services \| NIH \| National Cancer Institute (NCI); NU-21-08-00023 Agentura Pro Zdravotnický Výzkum České Republiky (Czech Health Research Council)
تواريخ الأحداث:	Date Created: 20240705 Latest Revision: 20240705
رمز التحديث:	20240706
DOI:	10.1038/s41416-024-02774-9
PMID:	38969867
قاعدة البيانات:	MEDLINE

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تدمد:	1532-1827
DOI:	10.1038/s41416-024-02774-9