Growth factor signalling and resistance to selective oestrogen receptor modulators and pure anti-oestrogens: the use of anti-growth factor therapies to treat or delay endocrine resistance in breast cancer.
De novo insensitivity and acquired resistance to the selective oestrogen receptor modulator tamoxifen and the pure anti-oestrogen fulvestrant (faslodex) severely limit their effectiveness in breast cancer patients. This is a major clinical problem, since each year upward of 1 million women are dispensed anti-oestrogenic drugs. In order to investigate the phenomenon of anti-oestrogen resistance and to rapidly screen drugs that target the resistance mechanism(s), we have previously established several in vitro breast cancer models that have acquired resistance to anti-hormones. Such cells commonly develop an ability to proliferate after approximately 3 months of exposure to 4-hydroxytamoxifen or fulvestrant, despite an initial endocrine-responsive (i.e. growth-suppressive) phase. The current paper explores the role that growth factor signalling plays in the transition of oestrogen receptor-positive endocrine-responsive breast cancer cells to anti-oestrogen resistance or insensitivity and how we might, in the future, most effectively use anti-growth factor therapies to treat or delay endocrine-resistant states.
Nicholson
R I
RI
Tenovus Centre for Cancer Research, Welsh School of Pharmacy, Cardiff University, Cardiff, UK. nicholsonri@cardiff.ac.uk
Hutcheson
I R
IR
Hiscox
S E
SE
Knowlden
J M
JM
Giles
M
M
Barrow
D
D
Gee
J M W
JM
D001943:Breast Neoplasms / Q000188:drug therapy*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004359:Drug Therapy, Combination; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D005260:Female; D006131:Growth Inhibitors / Q000627:therapeutic use*; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D010766:Phosphorylation; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects
D004965:Estrogen Antagonists; D006131:Growth Inhibitors; D006133:Growth Substances; D011956:Receptors, Cell Surface; D020845:Selective Estrogen Receptor Modulators