Unraveling the complexity of endocrine resistance in breast cancer by functional genomics.
Despite the proven benefit of antiestrogen drugs in breast cancer treatment, resistant disease ultimately develops in advanced breast cancer. In this issue of Cancer Cell, Iorns et al. find that loss of CDK10 expression promotes resistance of cells to tamoxifen and is associated with poor outcome in breast cancer patients treated with the drug. CDK10 loss increases the activity of the transcription factor ETS2 on the promoter of the RAF1 gene, elevating ERK/MAPK kinase pathway activity and relieving tamoxifen-induced G1 arrest. CDK10 is thus a potential biomarker for sensitivity in prospective clinical trials of patients treated with endocrine therapies.
Swanton
Charles
C
Cancer Research UK London Research Institute, Signal Transduction Laboratory, 44 Lincoln's Inn Fields, London WC2A 3PX, UK. swanton@cancer.org.uk <swanton@cancer.org.uk>
Downward
Julian
J
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics*; D004967:Estrogens / Q000172:deficiency; D023281:Genomics; D006801:Humans; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology / Q000627:therapeutic use; D014157:Transcription Factors / Q000378:metabolism
D018931:Antineoplastic Agents, Hormonal; D004268:DNA-Binding Proteins; C107465:ERF protein, human; D004967:Estrogens; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D014157:Transcription Factors; D013629:Tamoxifen; D019908:Proto-Oncogene Proteins c-raf; C501013:CDK10 protein, human; D018844:Cyclin-Dependent Kinases