Τίτλος:
Mechanisms of resistance to cyclin-dependent kinase 4/6 inhibitors
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Cyclin-dependent kinase (CDK) 4/6 inhibitors have emerged in the treatment of metastatic hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. However, most patients will eventually present disease progression, highlighting the inevitable resistance of cancer cells to CDK4/6 inhibition. Several studies have suggested that resistance mechanisms involve aberrations of the molecules that regulate the cell cycle, and the re-wiring of the cell to escape CDK4/6 dependence and turn to alternative pathways. Loss of retinoblastoma function, overexpression of CDK 6, upregulation of cyclin E, overexpression of CDK 7, and dysregulation of several signaling pathways, notably the PI3/AKT/mTOR pathway, have been implicated in the development of resistance to CDK4/6 inhibitors. Overlap with endocrine resistance mechanisms might be possible. Combinational therapeutic strategies should be explored in order to prevent resistance and optimize the management of patients after progression under CDK 4/6 inhibition. © 2021, The Author(s), under exclusive licence to Springer Nature B.V. part of Springer Nature.
Συγγραφείς:
Gomatou, G.
Trontzas, I.
Ioannou, S.
Drizou, M.
Syrigos, N.
Kotteas, E.
Περιοδικό:
Current Molecular Biology Reports
Εκδότης:
Springer Science and Business Media B.V.
Λέξεις-κλειδιά:
aurora A kinase; cyclin D1; cyclin D2; cyclin D3; cyclin dependent kinase 4; cyclin dependent kinase 6; cyclin dependent kinase 7; cyclin E; protein p53; retinoblastoma protein; antineoplastic agent; CCNE1 protein, human; CDK4 protein, human; CDK6 protein, human; cyclin dependent kinase; cyclin dependent kinase 4; cyclin dependent kinase 6; cyclin E; cyclin-dependent kinase-activating kinase; epidermal growth factor receptor 2; ERBB2 protein, human; MTOR protein, human; oncoprotein; protein kinase inhibitor; retinoblastoma protein; target of rapamycin kinase, Akt signaling; breast cancer; cell cycle; enzyme inhibition; enzyme mechanism; hormonal therapy; human; nonhuman; pathogenesis; Review; upregulation; breast tumor; disease exacerbation; drug effect; drug resistance; female; gene expression regulation; genetics; metabolism; molecularly targeted therapy; pathology; procedures; signal transduction, Antineoplastic Agents; Breast Neoplasms; Cell Cycle; Cyclin E; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Cyclin-Dependent Kinases; Disease Progression; Drug Resistance, Neoplasm; Female; Gene Expression Regulation, Neoplastic; Humans; Molecular Targeted Therapy; Oncogene Proteins; Protein Kinase Inhibitors; Receptor, ErbB-2; Retinoblastoma Protein; Signal Transduction; TOR Serine-Threonine Kinases
DOI:
10.1007/s11033-020-06100-3
