Abstract
Ovarian cancer is still the deadliest of all gynecologic malignancies in women worldwide. This is attributed to two main features of these tumors, namely, (i) a diagnosis at an advanced tumor stage, and, (ii) the rapid onset of resistance to standard chemotherapy after an initial successful therapy with platin- and taxol-derivatives. Therefore, novel targets for an early diagnosis and better treatment options for these tumors are urgently needed. Epidemiological data show that induction and biology of ovarian cancer is related to life-time estrogen exposure. Also experimental data reveal that ovarian cancer cells share a number of estrogen regulated pathways with other hormone-dependent cancers, e.g., breast and endometrial cancer. However, ovarian cancer is a heterogeneous disease and the subtypes are quite different with respect to mutations, origins, behaviors, markers, and prognosis and respond differently to standard chemotherapy. Therefore, a characterization of ovarian cancer subtypes may lead to better treatment options for the various subtypes and in particular for the most frequently observed high-grade serous ovarian carcinoma. For this intention, further studies on estrogen-related pathways and estrogen formation in ovarian cancer cells are warranted. The review gives an overview on ovarian cancer subtypes and explains the role of estrogen in ovarian cancer. Furthermore, enzymes active to synthesize and metabolize estrogens are described and strategies to target these pathways are discussed.
Highlights
The still poor prognosis for ovarian cancer is partly attributed to the fact that the diagnosis is usually made at a late stage, when the cancer has already spread to other organs
Local estrogen synthesis from circulating steroid hormone precursors by steroid-forming and steroid-inactivating enzymes may be important to drive ovarian cancer progression in women after the menopause. These enzymes and receptors were identified in ovarian cancer cells and their expression was shown to be related to clinical parameters
Such studies were mostly done in a small group of patients, which were not selected based on their age, ovarian cancer subtype, hormone-receptor status, and resistance to standard chemotherapy
Summary
A characterization of ovarian cancer subtypes may lead to better treatment options for the various subtypes and in particular for the most frequently observed high-grade serous ovarian carcinoma For this intention, further studies on estrogen-related pathways and estrogen formation in ovarian cancer cells are warranted. The majority of women experience a variety of non-specific symptoms in the year before diagnosis, the disease is not commonly recognized until the tumor reaches an advanced stage Another problem is the early development of resistance to the standard chemotherapy regimens with cisplatin/oxaliplatin in combination with paclitaxel. Experimental data demonstrated that ovarian cancer cells share a number of estrogen regulated pathways with other hormone-dependent cancers such as breast and endometrial cancer Such pathways were studied in more details already in these tumors [5,6,7].
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