Johnston, S. R. D., Martin, L. A., Leary, A., Head, J., Dowsett, M. (2007) Clinical strategies for rationale combinations of aromatase inhibitors with novel therapies for breast cancer. JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 106 (1–5). pp. 180-186. ISSN 0960-0760

Full text not available from this repository.

Abstract

Improving endocrine responsiveness and preventing the development of resistance is the goal of many current strategies that are looking to combine aromatase inhibitors with novel drugs that target various pathways in estrogen receptor (ER) positive breast cancer. Pre-clinical models of acquired resistance to aromatase inhibitors have suggested an increase in several signaling pathways including peptide growth factor signaling (EGFR, HER2) and activation of the mTOR signaling pathway. These may result in associated 'cross-talk' activation of ER-dependent gene transcription, such that dual blockade of ER together with other signaling pathways has become a logical approach to improve endocrine responsivness. Clinical strategies with aromatase inhibitors are looking to prevent activation of these pathways either through combination with the selective ER downregulator fulvestrant, or with various signal transduction inhibitors (STIs) including monoclonal antibodies (trastuzumab), small molecule tyrosine kinase inhibitors (TKIs) against EGFR or HER2 (lapatinib, gefitinib) and mTOR antagonists (temsirolimus). Early clinical data have emerged this year for some of these approaches with mixed results. This article reviews the rationale for these strategies, and discusses the lessons that need to be learnt if we are to successfully integrate these new drugs with aromatase inhibitors in the clinic. (C) 2007 Elsevier Ltd. All rights reserved.

Item Type:	Article
Authors (ICR Faculty only):	Martin, Lesley-Ann and Dowsett, Mitch and Johnston, Stephen
All Authors:	Johnston, S. R. D., Martin, L. A., Leary, A., Head, J., Dowsett, M.
Uncontrolled Keywords:	aromatase inhibitors; endocrine resistance; fulvestrant; signal transduction inhibitors; clinical trials; endpoints TERM ESTROGEN DEPRIVATION; NEOADJUVANT ENDOCRINE THERAPY; ACTIVATED PROTEIN-KINASE; PHASE-II; CELL-PROLIFERATION; MOLECULAR-CHANGES; RANDOMIZED-TRIAL; AKT ACTIVITY; MCF-7 CELLS; CROSS-TALK
Research teams:	Clinical Units > Breast Unit ICR divisions > Breast Cancer Research > Endocrinology ICR divisions > Molecular Pathology > Endocrinology
Depositing User:	Users 10 not found.
Date Deposited:	26 Nov 2007 13:28
Last Modified:	07 Feb 2014 15:21
URI:	http://publications.icr.ac.uk/id/eprint/5398

Actions (login required)

View Item