| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Professorial Unit of Surgery, City Hospital, Nottingham, UK
1 Tenovus Centre for Cancer Research, Welsh School of Pharmacy, Redwood Building, Cardiff University, Cardiff, UK
(Requests for offprints should be addressed to J F R Robertson; Email: john.robertson{at}nottingham.ac.uk)
This paper was presented at the 1st Tenovus/AstraZeneca Workshop, Cardiff (2005). AstraZeneca has supported the publication of these proceedings.
Studies of cell models and profiling of clinical breast cancer material to reveal the mechanisms of resistance to anti-oestrogen therapy, and to tamoxifen in particular, have reported that this phenomenon can be associated with increased expression and signalling through erbB Type 1 growth factor receptors, notably the epidermal growth factor receptor (EGFR) and HER2. Further molecular studies have revealed an intricate interlinking between such growth factor receptor pathways and oestrogen receptor (ER) signalling. Inhibition of receptor tyrosine kinase activity involved in the EGFR signalling cascade forms the basis for the use of EGFR specific tyrosine kinase inhibitors exemplified by gefitinib (ZD1839, Iressa) and erlotinib (OSI-774, Tarceva). Such agents have proved promising in pre-clinical studies and are currently in clinical trials in breast cancer, where gefitinib has been studied more extensively to date. Here, we present an overview of the current development of gefitinib in clinical breast cancer. This includes results from our clinical breast cancer trial 1839IL/0057 that demonstrate the efficacy of gefitinib within ER-positive, tamoxifen-resistant patients with locally advanced/metastatic disease, where parallel decreases in EGFR signal transduction and the Ki67 (MIB1) proliferation marker can be detected as predicted from model system studies. We also consider trials examining combination treatment with gefitinib and anti-hormonal strategies that will begin to address the clinically important question of whether gefitinib can delay/prevent onset of anti-hormone resistance.
This article has been cited by other articles:
|
|
 |
|
  A. Vazquez-Martin, C. Oliveras-Ferraros, R. Colomer, J. Brunet, and J. A. Menendez Low-scale phosphoproteome analyses identify the mTOR effector p70 S6 kinase 1 as a specific biomarker of the dual-HER1/HER2 tyrosine kinase inhibitor lapatinib (Tykerb(R)) in human breast carcinoma cells Ann. Onc., June 1, 2008; 19(6): 1097 - 1109. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. E Jones, J. M W Gee, I. R Hutcheson, J. M Knowlden, D. Barrow, and R. I Nicholson Growth factor receptor interplay and resistance in cancer Endocr. Relat. Cancer, December 1, 2006; 13(Supplement_1): S45 - S51. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Catania, T. M. De Pas, G. Pelosi, M. Manzotti, L. Adamoli, F. Nole, and A. Goldhirsch Erlotinib-Induced Breast Cancer Regression Ann. Pharmacother., November 1, 2006; 40(11): 2043 - 2047. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J M W Gee, A Howell, W J Gullick, C C Benz, R L Sutherland, R J Santen, L-A Martin, F Ciardiello, W R Miller, M Dowsett, et al. Consensus Statement Endocr. Relat. Cancer, July 1, 2005; 12(Supplement_1): S1 - S7. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R I Nicholson, I R Hutcheson, S E Hiscox, J M Knowlden, M Giles, D Barrow, and J M W Gee 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 Endocr. Relat. Cancer, July 1, 2005; 12(Supplement_1): S29 - S36. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
