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Genomic Aberrations that Activate D-type Cyclins Are Associated with Enhanced Sensitivity to the CDK4 and CDK6 Inhibitor Abemaciclib
- Source :
- Cancer Cell. 32:761-776.e6
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
Abstract
- Summary Most cancers preserve functional retinoblastoma (Rb) and may, therefore, respond to inhibition of D-cyclin-dependent Rb kinases, CDK4 and CDK6. To date, CDK4/6 inhibitors have shown promising clinical activity in breast cancer and lymphomas, but it is not clear which additional Rb-positive cancers might benefit from these agents. No systematic survey to compare relative sensitivities across tumor types and define molecular determinants of response has been described. We report a subset of cancers highly sensitive to CDK4/6 inhibition and characterized by various genomic aberrations known to elevate D-cyclin levels and describe a recurrent CCND1 3′UTR mutation associated with increased expression in endometrial cancer. The results suggest multiple additional classes of cancer that may benefit from CDK4/6-inhibiting drugs such as abemaciclib.
- Subjects :
- 0301 basic medicine
Cancer Research
Aminopyridines
Mice, Nude
Antineoplastic Agents
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Breast cancer
Cyclin D1
CDKN2A
Cyclin D
Neoplasms
medicine
Animals
Humans
Abemaciclib
Cell Proliferation
Mice, Inbred BALB C
Clinical Trials, Phase I as Topic
biology
Retinoblastoma
Endometrial cancer
Cyclin-Dependent Kinase 4
Cancer
Cyclin-Dependent Kinase 6
medicine.disease
Xenograft Model Antitumor Assays
030104 developmental biology
Oncology
chemistry
030220 oncology & carcinogenesis
Cancer research
biology.protein
Benzimidazoles
Female
Cyclin-dependent kinase 6
Subjects
Details
- ISSN :
- 15356108
- Volume :
- 32
- Database :
- OpenAIRE
- Journal :
- Cancer Cell
- Accession number :
- edsair.doi.dedup.....6bf0aa6fc912e9e26c4aed0ea43f0749
- Full Text :
- https://doi.org/10.1016/j.ccell.2017.11.006