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Cyclin-dependent kinase 4 and 6 inhibitors for hormone receptor-positive breast cancer: past, present, and future
- Source :
- The Lancet. 395:817-827
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- Summary The development and approval of cyclin-dependent kinase (CDK) 4 and 6 inhibitors for hormone receptor-positive and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer represents a major milestone in cancer therapeutics. Three different oral CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib, have significantly improved progression-free survival by a number of months when combined with endocrine therapy. More recently, improvement in overall survival has been reported with ribociclib and abemaciclib. The toxicity profile of all three drugs is well described and generally easily manageable with dose reductions when indicated. More myelotoxicity is observed with palbociclib and ribociclib, but more gastrointestinal toxicity is observed with abemaciclib. Emerging data is shedding light on the resistance mechanisms associated with CDK4/6 inhibitors, including cell cycle alterations and activation of upstream tyrosine kinase receptors. A number of clinical trials are exploring several important questions regarding treatment sequencing, combinatorial strategies, and the use of CDK4/6 inhibitors in the adjuvant and neoadjuvant settings, thereby further expanding and refining the clinical application of CDK4/6 inhibitors for patients with breast cancer.
- Subjects :
- Breast Neoplasms
030204 cardiovascular system & hematology
Palbociclib
Receptor tyrosine kinase
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Breast cancer
Cyclin-dependent kinase
Humans
Medicine
030212 general & internal medicine
Protein Kinase Inhibitors
Abemaciclib
Clinical Trials as Topic
biology
Cyclin-dependent kinase 4
business.industry
Cell Cycle
Cyclin-Dependent Kinase 4
Cancer
Cyclin-Dependent Kinase 6
General Medicine
medicine.disease
Metastatic breast cancer
Receptors, Estrogen
chemistry
biology.protein
Cancer research
Female
Receptors, Progesterone
business
Forecasting
Subjects
Details
- ISSN :
- 01406736
- Volume :
- 395
- Database :
- OpenAIRE
- Journal :
- The Lancet
- Accession number :
- edsair.doi.dedup.....d11fb93d9aa2c2a22e88f8976c587ee9
- Full Text :
- https://doi.org/10.1016/s0140-6736(20)30165-3