New insights on the role of hormonal therapy in ovarian cancer
| Autor: | Arlene E. Garcia-Soto, Joyce M. Slingerland, Fiona Simpkins |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Cell cycle checkpoint
endocrine system diseases Antineoplastic Agents Hormonal medicine.drug_class Clinical Biochemistry Estrogen receptor Biochemistry Article Endocrinology medicine Humans Aromatase Molecular Biology Pharmacology Ovarian Neoplasms biology business.industry Organic Chemistry Cell Cycle Cell cycle medicine.disease female genital diseases and pregnancy complications Blockade Receptors Estrogen Estrogen Immunology biology.protein Cancer research Hormonal therapy Female business Ovarian cancer hormones hormone substitutes and hormone antagonists |
| Popis: | Ovarian cancer (OVCA) is the most lethal gynecological malignancy. It is often diagnosed in advanced stages and despite therapy, 70% relapse within 2 years with incurable disease. Regimens with clinical benefit and minimal toxicity are urgently needed. More effective hormonal therapies would be appealing in this setting. Estrogens (E2) are implicated in the etiology of OVCA. Estrogens drive proliferation and anti-estrogens inhibit ovarian cancer growth in vitro and in vivo. Despite estrogen receptor (ER) expression in 67% of OVCAs, small anti-estrogen therapy trials have been disappointing and the benefit of hormonal therapy has not been systematically studied in large well-designed trials. OVCAs often manifest de novo anti-estrogen resistance and those that initially respond invariably develop resistance. Estrogens stimulate ovarian cancer progression by transcriptional activation and cross talk between liganded ER and mitogenic pathways, both of which drive cell cycle progression. Estrogen deprivation and estrogen receptor (ER) blockade cause cell cycle arrest in susceptible OVCAs by increasing the cell cycle inhibitor, p27. This review summarizes and discusses scientific and epidemiological evidence supporting estrogen’s role in ovarian carcinogenesis, provides an overview of clinical trials of ER blockade and aromatase inhibitors in OVCA and reviews potential causes of antiestrogen resistance. Anti-estrogen resistance was recently shown to be reversed by dual ER and Src signaling blockade. Blocking cross-talk between ER and constitutively activated kinase pathways may improve anti-estrogen therapeutic efficacy in OVCA, as has been demonstrated in other cancers. Novel strategies to improve benefit from anti-estrogens by combining them with targeted therapies are reviewed. |
| Databáze: | OpenAIRE |
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