Glucose Metabolic Reprogramming of ER Breast Cancer in Acquired Resistance to the CDK4/6 Inhibitor Palbociclib<sup>+</sup>
The majority of breast cancers express the estrogen receptor (ER) and are dependent on estrogen for their growth and survival. Endocrine therapy (ET) is the standard of care for these tumors. However, a superior outcome is achieved in a subset of ER positive (ER<sup>+</sup>)/human epider...
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| Format: | Article |
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MDPI AG
2020-03-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/3/668 |
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| author | Nicla Lorito Marina Bacci Alfredo Smiriglia Michele Mannelli Matteo Parri Giuseppina Comito Luigi Ippolito Elisa Giannoni Martina Bonechi Matteo Benelli Ilenia Migliaccio Luca Malorni Paola Chiarugi Andrea Morandi |
| author_facet | Nicla Lorito Marina Bacci Alfredo Smiriglia Michele Mannelli Matteo Parri Giuseppina Comito Luigi Ippolito Elisa Giannoni Martina Bonechi Matteo Benelli Ilenia Migliaccio Luca Malorni Paola Chiarugi Andrea Morandi |
| author_sort | Nicla Lorito |
| collection | DOAJ |
| description | The majority of breast cancers express the estrogen receptor (ER) and are dependent on estrogen for their growth and survival. Endocrine therapy (ET) is the standard of care for these tumors. However, a superior outcome is achieved in a subset of ER positive (ER<sup>+</sup>)/human epidermal growth factor receptor 2 negative (HER2<sup>−</sup>) metastatic breast cancer patients when ET is administrated in combination with a cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor, such as palbociclib. Moreover, CDK4/6 inhibitors are currently being tested in ER<sup>+</sup>/HER2<sup>+</sup> breast cancer and reported encouraging results. Despite the clinical advances of a combinatorial therapy using ET plus CDK4/6 inhibitors, potential limitations (i.e., resistance) could emerge and the metabolic adaptations underlying such resistance warrant further elucidation. Here we investigate the glucose-dependent catabolism in a series of isogenic ER<sup>+</sup> breast cancer cell lines sensitive to palbociclib and in their derivatives with acquired resistance to the drug. Importantly, ER<sup>+</sup>/HER2<sup>−</sup> and ER<sup>+</sup>/HER2<sup>+</sup> cell lines show a different degree of glucose dependency. While ER<sup>+</sup>/HER2<sup>−</sup> breast cancer cells are characterized by enhanced aerobic glycolysis at the time of palbociclib sensitivity, ER<sup>+</sup>/HER2<sup>+</sup> cells enhance their glycolytic catabolism at resistance. This metabolic phenotype was shown to have prognostic value and was targeted with multiple approaches offering a series of potential scenarios that could be of clinical relevance. |
| first_indexed | 2024-03-12T07:18:32Z |
| format | Article |
| id | doaj.art-c885404807d0449fbe83933f4de94acc |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T07:18:32Z |
| publishDate | 2020-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-c885404807d0449fbe83933f4de94acc2023-09-02T22:39:50ZengMDPI AGCells2073-44092020-03-019366810.3390/cells9030668cells9030668Glucose Metabolic Reprogramming of ER Breast Cancer in Acquired Resistance to the CDK4/6 Inhibitor Palbociclib<sup>+</sup>Nicla Lorito0Marina Bacci1Alfredo Smiriglia2Michele Mannelli3Matteo Parri4Giuseppina Comito5Luigi Ippolito6Elisa Giannoni7Martina Bonechi8Matteo Benelli9Ilenia Migliaccio10Luca Malorni11Paola Chiarugi12Andrea Morandi13Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Morgagni 50, I-50134 Florence, ItalyDepartment of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Morgagni 50, I-50134 Florence, ItalyDepartment of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Morgagni 50, I-50134 Florence, ItalyDepartment of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Morgagni 50, I-50134 Florence, ItalyDepartment of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Morgagni 50, I-50134 Florence, ItalyDepartment of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Morgagni 50, I-50134 Florence, ItalyDepartment of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Morgagni 50, I-50134 Florence, ItalyDepartment of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Morgagni 50, I-50134 Florence, ItalyTranslational Research Unit, Azienda USL Toscana Centro, Hospital of Prato, Via Suor Niccolina Infermiera 20, I-59100 Prato, ItalyBioinformatics Unit, Azienda USL Toscana Centro, Hospital of Prato, Via Suor Niccolina Infermiera 20, I-59100 Prato, ItalyTranslational Research Unit, Azienda USL Toscana Centro, Hospital of Prato, Via Suor Niccolina Infermiera 20, I-59100 Prato, ItalyTranslational Research Unit, Azienda USL Toscana Centro, Hospital of Prato, Via Suor Niccolina Infermiera 20, I-59100 Prato, ItalyDepartment of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Morgagni 50, I-50134 Florence, ItalyDepartment of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Morgagni 50, I-50134 Florence, ItalyThe majority of breast cancers express the estrogen receptor (ER) and are dependent on estrogen for their growth and survival. Endocrine therapy (ET) is the standard of care for these tumors. However, a superior outcome is achieved in a subset of ER positive (ER<sup>+</sup>)/human epidermal growth factor receptor 2 negative (HER2<sup>−</sup>) metastatic breast cancer patients when ET is administrated in combination with a cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor, such as palbociclib. Moreover, CDK4/6 inhibitors are currently being tested in ER<sup>+</sup>/HER2<sup>+</sup> breast cancer and reported encouraging results. Despite the clinical advances of a combinatorial therapy using ET plus CDK4/6 inhibitors, potential limitations (i.e., resistance) could emerge and the metabolic adaptations underlying such resistance warrant further elucidation. Here we investigate the glucose-dependent catabolism in a series of isogenic ER<sup>+</sup> breast cancer cell lines sensitive to palbociclib and in their derivatives with acquired resistance to the drug. Importantly, ER<sup>+</sup>/HER2<sup>−</sup> and ER<sup>+</sup>/HER2<sup>+</sup> cell lines show a different degree of glucose dependency. While ER<sup>+</sup>/HER2<sup>−</sup> breast cancer cells are characterized by enhanced aerobic glycolysis at the time of palbociclib sensitivity, ER<sup>+</sup>/HER2<sup>+</sup> cells enhance their glycolytic catabolism at resistance. This metabolic phenotype was shown to have prognostic value and was targeted with multiple approaches offering a series of potential scenarios that could be of clinical relevance.https://www.mdpi.com/2073-4409/9/3/668palbociclibmetabolic reprogrammingbreast cancerwarburg metabolismresistance |
| spellingShingle | Nicla Lorito Marina Bacci Alfredo Smiriglia Michele Mannelli Matteo Parri Giuseppina Comito Luigi Ippolito Elisa Giannoni Martina Bonechi Matteo Benelli Ilenia Migliaccio Luca Malorni Paola Chiarugi Andrea Morandi Glucose Metabolic Reprogramming of ER Breast Cancer in Acquired Resistance to the CDK4/6 Inhibitor Palbociclib<sup>+</sup> Cells palbociclib metabolic reprogramming breast cancer warburg metabolism resistance |
| title | Glucose Metabolic Reprogramming of ER Breast Cancer in Acquired Resistance to the CDK4/6 Inhibitor Palbociclib<sup>+</sup> |
| title_full | Glucose Metabolic Reprogramming of ER Breast Cancer in Acquired Resistance to the CDK4/6 Inhibitor Palbociclib<sup>+</sup> |
| title_fullStr | Glucose Metabolic Reprogramming of ER Breast Cancer in Acquired Resistance to the CDK4/6 Inhibitor Palbociclib<sup>+</sup> |
| title_full_unstemmed | Glucose Metabolic Reprogramming of ER Breast Cancer in Acquired Resistance to the CDK4/6 Inhibitor Palbociclib<sup>+</sup> |
| title_short | Glucose Metabolic Reprogramming of ER Breast Cancer in Acquired Resistance to the CDK4/6 Inhibitor Palbociclib<sup>+</sup> |
| title_sort | glucose metabolic reprogramming of er breast cancer in acquired resistance to the cdk4 6 inhibitor palbociclib sup sup |
| topic | palbociclib metabolic reprogramming breast cancer warburg metabolism resistance |
| url | https://www.mdpi.com/2073-4409/9/3/668 |
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