Endocrine therapy: defining the path of least resistance.
One of the best-characterized oncogenic mechanisms in breast cancer is the aberrant activation of phosphatidylinositol-3-kinase, protein kinase B, and mammalian target of rapamycin signaling. In both endocrine-resistant disease and breast cancer stem cells, this is commonly caused by specific genetic lesions or amplification of key pathway components or both. These observations have generated two interesting hypotheses. Firstly, do these genetic anomalies provide clinically significant biomarkers predictive of endocrine resistance? Secondly, do tamoxifen-resistant breast cancer cells emerge from a stem-like cell population? New studies, published in Breast Cancer Research, raise the possibility that these hypotheses are intrinsically linked.
Cancer Epigenetics Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, 2010, NSW, Australia. a.stone@garvan.org.au.
Andrew
A
Stone
Wolfson Wohl Cancer Research Centre, University of Glasgow, Garscube Estate, Switchback Road, Glasgow, Bearsden, G61 1QH, Scotland. liz.musgrove@glasgow.ac.uk.
Elizabeth A
EA
Musgrove
D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D009154:Mutation; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D058539:Phosphatidylinositol 3-Kinase / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D013629:Tamoxifen / Q000627:therapeutic use*
D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases