| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
REVIEW |
1 Cell Biology and Preclinical Models,
2 Clinical Trials
3 Medical Oncology C Units, INT-Fondazione Pascale, Via Mariano Semmola 80131 Naples, Italy
4 Sbarro Institute for Cancer Research and Molecular Medicine, Department of Biology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania 19122, USA
(Requests for offprints should be addressed to N Normanno; Email: nicnorm{at}yahoo.com)
Tamoxifen has been the mainstay of hormonal therapy in both early and advanced breast cancer patients for approximately three decades. The availability of novel compounds such as aromatase inhibitors (AIs) and fulvestrant, with different mechanism of action, is changing the scenario of endocrine treatment of postmenopausal breast cancer patients. In this review article, we have summarized the current knowledge of the mechanisms of resistance to endocrine therapy, in order to derive information that might be useful for therapeutic intervention. We propose that resistance to endocrine therapy is a progressive, step-wise phenomenon induced by the selective pressure of hormonal agents, which leads breast cancer cells from an estrogen-dependent, responsive to endocrine manipulation phenotype to a non-responsive phenotype, and eventually to an estrogen-independent phenotype. In particular, evidence suggests for each ‘action’ introduced to block estrogen stimulation of breast cancer cells (i.e. treatment with anti-estrogen), there are one or more corresponding ‘reactions’ that tumor cells can use to escape our attempts to block their growth: estrogen hypersensitivity associated with increased transcriptional activity of estrogen receptor
(ER) and/or increased non-genomic activity of ER, estrogen supersensitivity, increased growth factor signaling, suppression of ER expression and finally estrogen independence. Activation of growth factor signaling is involved in each step of this phenomenon, and might ultimately substitute estrogen in sustaining the growth and the survival of breast cancer cells. In this respect, results of pre-clinical and clinical studies with AIs, fulvestrant and signaling inhibitors sustain this hypothesis. More importantly, the knowledge of the mechanisms involved in the resistance of breast cancer cells to endocrine therapy offers potential for novel therapeutic strategies.
This article has been cited by other articles:
|
|
 |
|
  J. S. Samaddar, V. T. Gaddy, J. Duplantier, S. P. Thandavan, M. Shah, M. J. Smith, D. Browning, J. Rawson, S. B. Smith, J. T. Barrett, et al. A role for macroautophagy in protection against 4-hydroxytamoxifen-induced cell death and the development of antiestrogen resistance Mol. Cancer Ther., September 1, 2008; 7(9): 2977 - 2987. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Naresh, A. D. Thor, S. M. Edgerton, K. C. Torkko, R. Kumar, and F. E. Jones The HER4/4ICD Estrogen Receptor Coactivator and BH3-Only Protein Is an Effector of Tamoxifen-Induced Apoptosis Cancer Res., August 1, 2008; 68(15): 6387 - 6395. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Wang, S. Masri, S. Phung, and S. Chen The Role of Amphiregulin in Exemestane-Resistant Breast Cancer Cells: Evidence of an Autocrine Loop Cancer Res., April 1, 2008; 68(7): 2259 - 2265. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Ben-Jonathan, C. R. LaPensee, and E. W. LaPensee What Can We Learn from Rodents about Prolactin in Humans? Endocr. Rev., February 1, 2008; 29(1): 1 - 41. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Wu, D. R. Soler, M. C. Abba, M. I. Nunez, R. Baer, C. Hatzis, A. Llombart-Cussac, A. Llombart-Bosch, and C. M. Aldaz CtIP Silencing as a Novel Mechanism of Tamoxifen Resistance in Breast Cancer Mol. Cancer Res., December 1, 2007; 5(12): 1285 - 1295. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Georgy, J. Neceskas, and S. Goodin Antiemetic care for patients with breast cancer: Focus on drug interactions and safety concerns Am. J. Health Syst. Pharm., November 1, 2007; 64(21): 2227 - 2236. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Naughton, K. MacLeod, B. Kuske, R. Clarke, D. A. Cameron, and S. P. Langdon Progressive Loss of Estrogen Receptor {alpha} Cofactor Recruitment in Endocrine Resistance Mol. Endocrinol., November 1, 2007; 21(11): 2615 - 2626. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J W Assender, J M W Gee, I Lewis, I O Ellis, J F R Robertson, and R I Nicholson Protein kinase C isoform expression as a predictor of disease outcome on endocrine therapy in breast cancer J. Clin. Pathol., November 1, 2007; 60(11): 1216 - 1221. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Bartsch, C. Wenzel, G. Altorjai, U. Pluschnig, R. M. Mader, M. Gnant, R. Jakesz, M. Rudas, C. C. Zielinski, and G. G. Steger Her2 and Progesterone Receptor Status Are Not Predictive of Response to Fulvestrant Treatment Clin. Cancer Res., August 1, 2007; 13(15): 4435 - 4439. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Heldring, A. Pike, S. Andersson, J. Matthews, G. Cheng, J. Hartman, M. Tujague, A. Strom, E. Treuter, M. Warner, et al. Estrogen Receptors: How Do They Signal and What Are Their Targets Physiol Rev, July 1, 2007; 87(3): 905 - 931. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Trauernicht, S. J. Kim, N. H. Kim, and T. G. Boyer Modulation of Estrogen Receptor {alpha} Protein Level and Survival Function by DBC-1 Mol. Endocrinol., July 1, 2007; 21(7): 1526 - 1536. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Park, S. E. Aiyar, P. Fan, J. Wang, W. Yue, T. Okouneva, C. Cox, M. A. Jordan, L. Demers, H. Cho, et al. Effects of Tetramethoxystilbene on Hormone-Resistant Breast Cancer Cells: Biological and Biochemical Mechanisms of Action Cancer Res., June 15, 2007; 67(12): 5717 - 5726. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Kuske, C. Naughton, K. Moore, K. G MacLeod, W. R Miller, R. Clarke, S. P Langdon, and D. A Cameron Endocrine therapy resistance can be associated with high estrogen receptor {alpha} (ER{alpha}) expression and reduced ER{alpha} phosphorylation in breast cancer models Endocr. Relat. Cancer, December 1, 2006; 13(4): 1121 - 1133. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Lupu and J. A. Menendez Targeting Fatty Acid Synthase in Breast and Endometrial Cancer: An Alternative to Selective Estrogen Receptor Modulators? Endocrinology, September 1, 2006; 147(9): 4056 - 4066. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Pietras Biologic Basis of Sequential and Combination Therapies for Hormone-Responsive Breast Cancer Oncologist, July 1, 2006; 11(7): 704 - 717. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
