Modulation of epidermal growth factor receptor in endocrine-resistant, estrogen-receptor-positive breast cancer.
An increasing body of evidence demonstrates that growth factor networks are highly interactive with estrogen receptor signaling in the control of breast cancer growth. As such, tumor responses to antihormones are likely to be a composite of the estrogen receptor and growth factor inhibitory activity of these agents. The modulation of growth factor networks during endocrine response is examined, and in vitro and clinical evidence is presented that epidermal growth factor receptor signaling, maintained in either an estrogen receptor-dependent or a receptor-independent manner, is critical to antihormone-resistant breast cancer cell growth. The considerable potential of the epidermal growth factor receptor-selective tyrosine kinase inhibitor Iressa (ZD 1839) to efficiently treat, and perhaps even prevent, endocrine-resistant breast cancer is highlighted.
Nicholson
R I
RI
Tenovus Centre for Cancer Research, Welsh School of Pharmacy, Cardiff, Wales. nicholsonri@cardiff.ac.uk
Hutcheson
I R
IR
Harper
M E
ME
Knowlden
J M
JM
Barrow
D
D
McClelland
R A
RA
Jones
H E
HE
Wakeling
A E
AE
Gee
J M W
JM
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D004702:Endocrine Glands; D066246:ErbB Receptors / Q000378:metabolism*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D020847:Estrogen Receptor Modulators / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D000077156:Gefitinib; D006801:Humans; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011799:Quinazolines / Q000494:pharmacology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000502:physiology; D011960:Receptors, Estrogen / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013629:Tamoxifen / Q000494:pharmacology; D000068878:Trastuzumab; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D004958:Estradiol; D020847:Estrogen Receptor Modulators; D000077267:Fulvestrant; D000077156:Gefitinib; D011505:Protein-Tyrosine Kinases; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D013629:Tamoxifen; D000068878:Trastuzumab