Cells | |
Glucose Metabolic Reprogramming of ER Breast Cancer in Acquired Resistance to the CDK4/6 Inhibitor Palbociclib+ | |
Matteo Benelli1  Marina Bacci2  Paola Chiarugi2  Elisa Giannoni2  Matteo Parri2  Nicla Lorito2  Michele Mannelli2  Alfredo Smiriglia2  Andrea Morandi2  Giuseppina Comito2  Luigi Ippolito2  Ilenia Migliaccio3  Luca Malorni3  Martina Bonechi3  | |
[1] Bioinformatics Unit, Azienda USL Toscana Centro, Hospital of Prato, Via Suor Niccolina Infermiera 20, I-59100 Prato, Italy;Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Morgagni 50, I-50134 Florence, Italy;Translational Research Unit, Azienda USL Toscana Centro, Hospital of Prato, Via Suor Niccolina Infermiera 20, I-59100 Prato, Italy; | |
关键词: palbociclib; metabolic reprogramming; breast cancer; warburg metabolism; resistance; | |
DOI : 10.3390/cells9030668 | |
来源: DOAJ |
【 摘 要 】
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+)/human epidermal growth factor receptor 2 negative (HER2−) 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+/HER2+ 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+ breast cancer cell lines sensitive to palbociclib and in their derivatives with acquired resistance to the drug. Importantly, ER+/HER2− and ER+/HER2+ cell lines show a different degree of glucose dependency. While ER+/HER2− breast cancer cells are characterized by enhanced aerobic glycolysis at the time of palbociclib sensitivity, ER+/HER2+ 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.
【 授权许可】
Unknown