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Oestrogen/growth factor cross-talk in breast carcinoma: a specific target for novel antioestrogens
1Department of Preclinical Oncology, Istituto Nazionale per la Alcarca sul Cancro, Genova, Italy.
Abstract:
Breast cancer cells express receptors for and are sensitive to a variety of steroids, polypeptide hormones and growth factors; the blocking of and/or the interference with their biochemical pathways could represent a new approach to breast tumour therapy. Antioestrogens achieve such a goal by competing with oestradiol for binding to the oestrogen receptors through which intracellular effects of the hormone are mediated. Tamoxifen has undergone the most extensive clinical evaluations and represents the treatment of choice for the endocrine management of breast cancer. Nevertheless, it is well known that tamoxifen retains agonist activity both in vitro and in vivo. To circumvent this disadvantage, new molecules with steroid-like structure, represented by ICI 164,384 and ICI 182,780, have been synthesized. In this review, Alessandra de Cupis and Roberto Favoni review data about the cross-talk between the two major families of breast cancer growth regulator: oestrogens and growth factors, focusing on the use of nonsteroidal antioestrogens and the new generation of steroidal antioestrogens as possible specifically targeted inhibitors of breast tumour proliferation.
Insights
New antioestrogens offer targeted breast cancer therapy by blocking oestrogen and growth factor pathways. These novel agents, including steroidal antioestrogens, aim to inhibit tumour proliferation more effectively than tamoxifen.
Area of Science:
- Oncology
- Endocrinology
- Molecular Biology
Background:
- Breast cancer cells are influenced by steroids, hormones, and growth factors.
- Targeting these pathways offers a novel therapeutic approach for breast tumors.
- Antioestrogens, like tamoxifen, compete with oestradiol for oestrogen receptors.
Purpose of the Study:
- To review the cross-talk between oestrogens and growth factors in breast cancer.
- To focus on nonsteroidal and new-generation steroidal antioestrogens.
- To evaluate these agents as targeted inhibitors of breast tumour proliferation.
Main Methods:
- Review of existing data on antioestrogen mechanisms.
- Analysis of the biochemical pathways involved in breast cancer growth.
- Comparison of tamoxifen with newer steroidal antioestrogens (ICI 164,384 and ICI 182,780).
Main Results:
- Tamoxifen, while effective, exhibits undesirable agonist activity.
- New steroidal antioestrogens (ICI 164,384, ICI 182,780) were synthesized to overcome tamoxifen's limitations.
- Understanding the interplay between oestrogens and growth factors is crucial for targeted therapy.
Conclusions:
- Nonsteroidal and novel steroidal antioestrogens represent a promising strategy for targeted breast cancer treatment.
- These agents aim to specifically inhibit tumour proliferation by interfering with key growth pathways.
- Further research into these targeted inhibitors could lead to improved breast cancer therapies.