Inhibition of CDK8/19 Mediator kinase potentiates HER2-targeting drugs and bypasses resistance to these agents in vitro and in vivo.
Animals
Antineoplastic Agents
/ pharmacology
Breast Neoplasms
/ drug therapy
Cell Line, Tumor
Cyclin-Dependent Kinase 8
/ genetics
Cyclin-Dependent Kinases
/ metabolism
Drug Resistance, Neoplasm
/ drug effects
Female
Humans
Lapatinib
/ pharmacology
Mice
Phosphatidylinositol 3-Kinases
/ metabolism
Protein Kinase Inhibitors
/ pharmacology
Receptor, ErbB-2
/ metabolism
Trastuzumab
/ metabolism
Xenograft Model Antitumor Assays
CDK8/19
HER2
Mediator kinase
lapatinib
trastuzumab
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
09 08 2022
09 08 2022
Historique:
entrez:
1
8
2022
pubmed:
2
8
2022
medline:
4
8
2022
Statut:
ppublish
Résumé
Breast cancers (BrCas) that overexpress oncogenic tyrosine kinase receptor HER2 are treated with HER2-targeting antibodies (such as trastuzumab) or small-molecule kinase inhibitors (such as lapatinib). However, most patients with metastatic HER2
Identifiants
pubmed: 35914167
doi: 10.1073/pnas.2201073119
pmc: PMC9371674
doi:
Substances chimiques
Antineoplastic Agents
0
Protein Kinase Inhibitors
0
Lapatinib
0VUA21238F
BTG2 protein, human
141490-22-4
Receptor, ErbB-2
EC 2.7.10.1
CDK19 protein, human
EC 2.7.11.22
CDK8 protein, human
EC 2.7.11.22
Cyclin-Dependent Kinase 8
EC 2.7.11.22
Cyclin-Dependent Kinases
EC 2.7.11.22
Trastuzumab
P188ANX8CK
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2201073119Subventions
Organisme : NIGMS NIH HHS
ID : P20 GM109091
Pays : United States
Organisme : NCI NIH HHS
ID : R43 CA221485
Pays : United States
Organisme : NCI NIH HHS
ID : R44 CA203184
Pays : United States
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