Academic Journal
Targeting mTOR to overcome resistance to hormone and CDK4/6 inhibitors in ER-positive breast cancer models
| العنوان: | Targeting mTOR to overcome resistance to hormone and CDK4/6 inhibitors in ER-positive breast cancer models |
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| المؤلفون: | Rodriguez, María Jimena, Perrone, María Cecilia, Riggio, Marina, Palafox Sánchez, Marta, Salinas, Valeria, Elia, Andres, Serra Elizalde, Violeta |
| المساهمون: | Institut Català de la Salut, Rodriguez MJ, Perrone MC, Riggio M, Elia A Instituto de Biología y Medicina Experimental (IBYME-CONICET), Protein Kinases and Cancer Laboratory, Buenos Aires, Argentina. Palafox M, Serra V Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Salinas V Hospital JM Ramos Mejía, Neurogenetics Unit, Buenos Aires, Argentina. Universidad Austral, Translational Medicine Research Institute IIMT-CONICET, Buenos Aires, Provincia de Buenos Aires, Argentina, Vall d'Hebron Barcelona Hospital Campus |
| المصدر: | Scientia |
| بيانات النشر: | Nature Portfolio |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Mama - Càncer - Tractament, Resistència als medicaments, Proteïnes quinases - Inhibidors - Ús terapèutic, DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms, Other subheadings::Other subheadings::/therapy, PHENOMENA AND PROCESSES::Physiological Phenomena::Pharmacological and Toxicological Phenomena::Pharmacological Phenomena::Drug Resistance::Drug Resistance, Neoplasm, CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protein Kinase Inhibitors, Other subheadings::Other subheadings::/therapeutic use, ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama, Otros calificadores::Otros calificadores::/terapia, FENÓMENOS Y PROCESOS::fenómenos fisiológicos::fenómenos farmacológicos y toxicológicos::fenómenos farmacológicos::resistencia a medicamentos::resistencia a los antineoplásicos, COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::inhibidores enzimáticos::inhibidores de proteínas cinasas, Otros calificadores::Otros calificadores::/uso terapéutico |
| الوصف: | Cancer; Cell biology ; Càncer; Biologia cel·lular ; Cáncer; Biología celular ; Resistance to therapy remains a major obstacle in cancer management. Although treatment with hormone and CDK4/6 inhibitors is successful in luminal breast cancer, resistance to these treatments is frequent, highlighting the need for novel therapeutic strategies to delay disease progression and improve patient survival. Here, we assessed the mechanisms of acquired resistance using T47D and MCF-7 tamoxifen- and palbociclib-resistant cell-line variants in culture and as xenografts, and patient-derived cells (PDCs) obtained from sensitive or resistant patient-derived xenografts (PDXs). In these models, we analyzed the effect of specific kinase inhibitors on survival, signaling and cellular aggressiveness. Our results revealed that mTOR inhibition is more effective than PI3K inhibition in overcoming resistance, irrespective of PIK3CA mutation status, by decreasing cell proliferation and tumor growth, as well as reducing cell migration and stemness. Moreover, a combination of mTOR and CDK4/6 inhibitors may prevent pathway reactivation downstream of PI3K, interfering with the survival of resistant cells and consequent tumor escape. In conclusion, we highlight the benefits of incorporating mTOR inhibitors into the current therapy in ER + breast cancer. This alternative therapeutic strategy not only enhances the antitumor response but may also delay the emergence of resistance and tumor recurrence. ; This work was supported by CONICET, ANPCYT (Grants PICT2509 & PICT0345), Instituto Nacional del Cáncer (Grants 2016 & 2018), Fundación Williams, Fundación Bunge & Born (Oster Grant) (Argentina); Instituto de Salud Carlos III (Grants PI20/00892 & CPII19/0033), Ministerio de Economía y Competitividad (FJCI-2015-25412) (Spain). |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2045-2322 |
| Relation: | Scientific Reports;13; https://doi.org/10.1038/s41598-023-29425-y; info:eu-repo/grantAgreement/ES/PEICTI2021-2023/PI20%2F00892; info:eu-repo/grantAgreement/ES/PE2013-2016/FJCI-2015-25412; info:eu-repo/grantAgreement/ES/PE2017-2020/CPII19%2F00033; Rodriguez MJ, Perrone MC, Riggio M, Palafox M, Salinas V, Elia A, et al. Targeting mTOR to overcome resistance to hormone and CDK4/6 inhibitors in ER-positive breast cancer models. Sci Rep. 2023 Feb 15;13:2710.; https://hdl.handle.net/11351/9169 |
| DOI: | 10.1038/s41598-023-29425-y |
| الاتاحة: | https://hdl.handle.net/11351/9169 https://doi.org/10.1038/s41598-023-29425-y |
| Rights: | Attribution 4.0 International ; http://creativecommons.org/licenses/by/4.0/ ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.3C4081F3 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 20452322 |
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| DOI: | 10.1038/s41598-023-29425-y |