Mechanisms of resistance to cyclin-dependent kinase 4/6 inhibitors.
Antineoplastic Agents
/ therapeutic use
Breast Neoplasms
/ drug therapy
Cell Cycle
/ drug effects
Cyclin E
/ genetics
Cyclin-Dependent Kinase 4
/ antagonists & inhibitors
Cyclin-Dependent Kinase 6
/ antagonists & inhibitors
Cyclin-Dependent Kinases
/ antagonists & inhibitors
Disease Progression
Drug Resistance, Neoplasm
/ drug effects
Female
Gene Expression Regulation, Neoplastic
Humans
Molecular Targeted Therapy
/ methods
Oncogene Proteins
/ genetics
Protein Kinase Inhibitors
/ therapeutic use
Receptor, ErbB-2
/ genetics
Retinoblastoma Protein
/ genetics
Signal Transduction
TOR Serine-Threonine Kinases
/ genetics
Cyclin-Dependent Kinase-Activating Kinase
Breast Cancer
CDK 4/6 inhibitors
Cyclin-dependent kinase
Resistance
Journal
Molecular biology reports
ISSN: 1573-4978
Titre abrégé: Mol Biol Rep
Pays: Netherlands
ID NLM: 0403234
Informations de publication
Date de publication:
Jan 2021
Jan 2021
Historique:
received:
06
08
2020
accepted:
16
12
2020
pubmed:
8
1
2021
medline:
21
5
2021
entrez:
7
1
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33409716
doi: 10.1007/s11033-020-06100-3
pii: 10.1007/s11033-020-06100-3
doi:
Substances chimiques
Antineoplastic Agents
0
CCNE1 protein, human
0
Cyclin E
0
Oncogene Proteins
0
Protein Kinase Inhibitors
0
Retinoblastoma Protein
0
MTOR protein, human
EC 2.7.1.1
ERBB2 protein, human
EC 2.7.10.1
Receptor, ErbB-2
EC 2.7.10.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
CDK4 protein, human
EC 2.7.11.22
CDK6 protein, human
EC 2.7.11.22
Cyclin-Dependent Kinase 4
EC 2.7.11.22
Cyclin-Dependent Kinase 6
EC 2.7.11.22
Cyclin-Dependent Kinases
EC 2.7.11.22
Cyclin-Dependent Kinase-Activating Kinase
EC 2.7.11.22
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
915-925Références
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