PMID- 26053278
OWN - NLM
STAT- MEDLINE
DCOM- 20151117
LR  - 20150725
IS  - 1473-5741 (Electronic)
IS  - 0959-4973 (Linking)
VI  - 26
IP  - 8
DP  - 2015 Sep
TI  - CDK4/6 inhibitors in breast cancer.
PG  - 797-806
LID - 10.1097/CAD.0000000000000249 [doi]
AB  - Deregulation of the cyclin-dependent kinase (CDK) 4/6-retinoblastoma (RB) axis 
      can occur through a number of mechanisms and contributes towards the unrestrained 
      growth witnessed in a variety of cancers including breast cancers. Recent years 
      have seen the development of selective CDK4/6 inhibitors, which have delivered 
      promising preclinical and clinical results in breast cancer and other tumours. A 
      number of trials assessing antitumour efficacy in various disease settings and 
      combinations are ongoing. The cyclin D1-CDK-Rb axis and its role in the cell 
      cycle of normal and cancer cells are delineated. The early pan-CDK inhibitor 
      flavopiridol and subsequent preclinical and clinical development of selective 
      CDK4/6 inhibitors are described. Ongoing studies in breast cancer with novel 
      CDK4/6 inhibitors (palbociclib, abemaciclib and ribociclib) are explored. A 
      literature search of these topics was performed through PubMed. Abstracts from 
      major oncology meetings were also reviewed. Selective CDK4/6 inhibitors, as 
      represented by the competing compounds currently in clinical development, 
      comprise a novel, safe and, thus far, promisingly efficacious group of drugs. 
      Considerable resources are being devoted towards exploring the efficacy of these 
      drugs in combination with endocrine therapies, an approach that has yielded 
      encouraging results and accelerated approval by the US Food and Drugs 
      Administration for one of these agents (palbociclib). The results of confirmatory 
      phase 3 trials are, however, awaited. We discuss further therapy combinations in 
      development and highlight potential areas for caution including the potential for 
      antagonistic interactions with cytotoxic chemotherapies.
FAU - Dukelow, Tim
AU  - Dukelow T
AD  - aDepartment of Medical Oncology, Bon Secours Hospital, Cork bSchool of Medicine, 
      University College Cork, Ireland cSchool of Medicine, Deakin University, Geelong, 
      Victoria dNHMRC CTC University of Sydney, New South Wales, Australia.
FAU - Kishan, Divya
AU  - Kishan D
FAU - Khasraw, Mustafa
AU  - Khasraw M
FAU - Murphy, Conleth G
AU  - Murphy CG
LA  - eng
PT  - Journal Article
PT  - Review
PL  - England
TA  - Anticancer Drugs
JT  - Anti-cancer drugs
JID - 9100823
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Protein Kinase Inhibitors)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 4)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 6)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/pharmacology/*therapeutic use
MH  - Breast Neoplasms/*drug therapy/metabolism
MH  - Clinical Trials as Topic
MH  - Cyclin-Dependent Kinase 4/*antagonists & inhibitors/metabolism
MH  - Cyclin-Dependent Kinase 6/*antagonists & inhibitors/metabolism
MH  - Female
MH  - Humans
MH  - Protein Kinase Inhibitors/pharmacology/*therapeutic use
EDAT- 2015/06/09 06:00
MHDA- 2015/11/18 06:00
CRDT- 2015/06/09 06:00
PHST- 2015/06/09 06:00 [entrez]
PHST- 2015/06/09 06:00 [pubmed]
PHST- 2015/11/18 06:00 [medline]
AID - 10.1097/CAD.0000000000000249 [doi]
PST - ppublish
SO  - Anticancer Drugs. 2015 Sep;26(8):797-806. doi: 10.1097/CAD.0000000000000249.