Cross-resistance to different aromatase inhibitors in breast cancer treatment.

1999 ◽  
pp. 251-257 ◽  
Author(s):  
P E L√∏nning
Keyword(s):  
Breast Cancer ◽  
Binding Site ◽  
Aromatase Inhibitors ◽  
Mechanism Of Action ◽  
Breast Cancer Treatment ◽  
Cross Resistance ◽  
Alternative Mechanism ◽  
Aromatase Inhibition ◽  
Future Studies ◽  
Enzyme Binding

Recent studies have documented the biochemical and clinical efficacy of novel aromatase inhibitors. These drugs belong to one of two classes: non-steroidal and steroidal drugs, known to be different with respect to enzyme binding site and their effect on the aromatase enzyme. Several studies have now confirmed a lack of complete cross-resistance to drugs of the two classes. While some of these observations may be explained by a more potent aromatase inhibition caused by some aormatase inhibitors compared to others, this is not always the case. Such observations therefore focus on the importance of alternative mechanism of action like a differential influence on the intratumour aromatase enzyme by the different drugs. Current and future studies should aim at exploring the mechanism of cross-resistance and evaluate optimal use of different aromatase inhibitors in sequence or probably, also in concert.

Aromatase Inhibitors for the Treatment of Breast Cancer: A Journey from the Scratch

2020 ◽  
Vol 20 (17) ◽  
pp. 1994-2004 ◽  
Author(s):  
Pooja Ratre ◽  
Keerti Mishra ◽  
Amit Dubey ◽  
Amber Vyas ◽  
Akhlesh Jain ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Treatment ◽  
Postmenopausal Women ◽  
Aromatase Inhibitors ◽  
3D Structure ◽  
Postmenopausal Breast Cancer ◽  
Breast Cancer Treatment ◽  
Third Generation ◽  
Breast Cancer Chemotherapy

Background: Estrogens are essential for the growth of breast cancer in the case of premenopausal as well as in postmenopausal women. However, most of the breast cancer incidences are reported in postmenopausal women and the concurrent risk surges with an increase in age. Since the enzyme aromatase catalyses essential steps in estrogen biosynthesis, Aromatase Inhibitors (AIs) are effective targeted therapy in patients with Estrogen Receptor positive (ER+) breast cancer. AIs are more effective than Selective Estrogen Receptor Modulators (SERMs) because they block both the genomic and nongenomic activities of ER. Till date, first, second and third-generation AIs have been approved by the FDA. The third-generation AIs, viz. Letrozole, Anastrozole, Exemestane, are currently used in the standard treatment for postmenopausal breast cancer. Methods: Data were collected from Medline, PubMed, Google Scholar, Science Direct through searching of keywords: ‘aromatase’, ‘aromatase inhibitors’, ‘breast cancer’, ‘steroidal aromatase inhibitors’, ‘non-steroidal inhibitors’ and ‘generations of aromatase inhibitors’. Results: In the current scenario of breast cancer chemotherapy, AIs are the most widely used agents which reveal optimum efficacy along with the least side effects. Keeping in view the prominence of AIs in breast cancer therapy, this review covered the detailed description of aromatase including its role in the biosynthesis of estrogen, biochemistry, gene expression, 3D-structure, and information of reported AIs along with their role in breast cancer treatment. Conclusion: AIs are the mainstream solution of the ER+ breast cancer treatment regimen with the continuous improvement of human understanding of the importance of a healthy life of women suffering from breast cancer.

scholarly journals Aromatase inhibitors in breast cancer.

2004 ◽  
Vol 11 (2) ◽  
pp. 179-189 ◽  
Author(s):  
P E L√∏nning
Keyword(s):  
Breast Cancer ◽  
Aromatase Inhibitors ◽  
Cancer Biology ◽  
Postmenopausal Breast Cancer ◽  
Phase Iii ◽  
Cross Resistance ◽  
Consistent Difference ◽  
Clinical Effects ◽  
Endocrine Regulation

The development of aromatase inhibitors for breast cancer therapy is a result of successful translational research exploring the biochemical effects of different compounds in vivo. Studies assessing plasma oestrogen levels as well as in vivo aromatase inhibition have revealed a consistent difference with respect to biochemical efficacy between the third generation compounds (anastrozole, letrozole and exemestane) and the previous, first and second generation drugs, corresponding to the improved clinical effects of these compounds as outlined in large phase III studies. Thus, endocrine evaluation has been found to be a valid surrogate parameter for clinical efficacy. Moreover, the results from these studies have added important biological information to our understanding of endocrine regulation of breast cancer. Based on the clinical results so far, aromatase inhibitors are believed to play a key role in future adjuvant therapy of postmenopausal breast cancer patients and potentially also for breast cancer prevention. Interesting findings such as the lack of cross-resistance between steroidal and non-steroidal compounds should be further explored, as this may add additional information to our understanding of breast cancer biology.

Novel Non-Steroidal Aromatase Inhibitors: Are There New Perspectives in the Treatment of Breast Cancer?

1996 ◽  
Vol 82 (5) ◽  
pp. 417-422 ◽  
Author(s):  
Emilio Bajetta ◽  
Luigi Celio ◽  
Roberto Buzzoni ◽  
Ettore Bichisao
Keyword(s):  
Breast Cancer ◽  
Aromatase Inhibitors ◽  
Advanced Disease ◽  
Malignant Neoplasm ◽  
Clinical Results ◽  
High Potency ◽  
Aromatase Inhibition ◽  
Oral Activity ◽  
Steroidal Aromatase Inhibitors ◽  
Orally Active

Breast cancer is the most common malignant neoplasm affecting women in Western countries, and most new cases are manifested during the postmenopausal period. The clinical results obtained with aminoglutethimide, and later with formestane, have established aromatase inhibition as one of the major therapeutic options in hormone-dependent advanced disease. Nevertheless, the lack of specificity of aminoglutethimide and the less than optimal oral activity of formestane soon led to further efforts to find a potent, highly selective, orally active, side-effect-free aromatase inhibitor for use in postmenopausal women with advanced breast cancer. Here we review the available data on three new, competitive non-steroidal aromatase inhibitors –- letrozole, vorozole and anastrozole –- which are approaching the point of detailed pharmacologic and clinical evaluation. Preliminary data have confirmed the high potency and selectivity of these endocrine agents, but their antitumor activity still remains to be completely defined. Challenges given by these novel aromatase inhibitors are discussed taking into account the biologic implications related to their mechanism of action and their future use in the management of breast cancer.

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