The biology of antihormone failure in breast cancer.
Many estrogen receptor-positive breast cancer patients initially respond to treatment with antihormonal agents such as tamoxifen, but remissions are often followed by acquisition of resistance and ultimately disease relapse. The development of a rationale for the effective treatment of tamoxifen-resistant breast cancer requires an understanding of the complex signal transduction mechanisms that contribute towards loss of antiestrogen response. Interactions between estrogen and growth factor signaling pathways have been identified in estrogen-responsive cells that are thought to reinforce their individual cellular effects on growth and gene responses. Increasing evidence indicates that abnormalities occurring in growth factor signaling pathways, notably the epidermal growth factor receptor (EGFR) signaling pathway, could dramatically influence steroid hormone action and may be critical to antihormonal-resistant breast cancer cell growth. Thus, inhibitory agents targeting growth factor receptors, or their intracellular pathway components, may prove clinically beneficial in antihormone refractory disease. One example, gefitinib ('Iressa', ZD1839), an EGFR-tyrosine kinase inhibitor, is an interesting therapeutic option that may provide benefit in the treatment of antihormonal-resistant breast cancer. Rapid progress with pharmacological and molecular therapeutic agents is now being made. Therapies that target growth factor signaling pathways may prevent development of resistance.
Nicholson
Robert I
RI
Tenovus Centre for Cancer Research, Welsh School of Pharmacy, Cardiff University, Cardiff, UK. nicholsonri@cardiff.ac.uk
Gee
Julia M W
JM
Knowlden
Janice
J
McClelland
Richard
R
Madden
Tracie-Ann
TA
Barrow
Denise
D
Hutcheson
Iain
I
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D000077156:Gefitinib; D006801:Humans; D009364:Neoplasm Recurrence, Local; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011799:Quinazolines / Q000494:pharmacology*; D015398:Signal Transduction
D018931:Antineoplastic Agents, Hormonal; D011799:Quinazolines; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D000077156:Gefitinib