The role of hormonal factors and endocrine therapy in ovarian cancer

Serkies, Krystyna; Sinacki, Marcin; Jassem, Jacek

doi:10.5114/wo.2013.33768

Cited by 7 publications

(6 citation statements)

References 45 publications

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“…More than 55% of ovarian cancers express ER on the cell surface (23,24). Although ER expression in ovarian cancer is similar to breast cancer, the efforts to target ER merely present a short-term benefit in ~28% of ovarian cancer cases (4,8,9).…”

Section: Discussionmentioning

confidence: 99%

An ovarian cancer model with positive ER: Reversion of ER antagonist resistance by Src blockade

Han

et al. 2014

Oncology Reports

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Approximately 60% of ovarian cancers are positive for the estrogen receptor (ER); however, ER-targeted treatment is disappointing due to drug resistance as compared with breast cancer. In estrogen-sensitive cancers, estrogen activates Src to phosphorylate p27 promoting its degradation and increasing cell cycle progression. Since Src is frequently activated in ovarian cancers, we investigated whether combined Src and ER blockade by saracatinib and fulvestrant would circumvent anti-estrogen resistance. In 20 out of 40 enrolled patients with immunohistochemically ER-positive ovarian cancer, phosphorylated Src (p-Src) at the site of 416 tyrosine was expressed with a propensity for metastasis and a poorer disease-free survival (DFS) at 3 years following ER antagonist treatment. The effects of ER and Src blockade on cell cycle were assayed in estrogen receptor α (ERα)-positive ovarian cancer. We observed that Src activity was fairly greater in anti-estrogen-resistant ovarian cancer cells than that in the anti-estrogen-sensitive cell line. Estrogen activated Src via ER-Src binding and ER translocation from cytoplasm to nucleus. Mitogenesis was mediated via ERα, not ERβ. Combined saracatinib and fulvestrant increased p27 and inhibited cell cycle progression. Furthermore, dual therapy induced autophagy and inhibited ovarian cancer xenograft growth more effectively than monotherapy. Saracatinib facilitated the therapeutic effects of fulvestrant by antagonizing the estrogen-mediated Src activation. These are supportive of further preclinical assessment of combined fulvestrant and saracatinib in patients with ovarian cancer.

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Section: Discussionmentioning

confidence: 99%

An ovarian cancer model with positive ER: Reversion of ER antagonist resistance by Src blockade

Han

et al. 2014

Oncology Reports

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“…The maintenance of homeostasis in a multicellular organism is associated with the balance between such processes as proliferation, differentiation and cell death. Ovarian cancer is most frequently diagnosed at an advanced stage [ 20 , 21 ]. In the diagnosis of changes in the differentiation of malignant cancer, it is very important to check the family history, biochemical markers and ultrasonography image (USG) [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of metformin on apoptosis induction in ovarian cancer cells

Rogalska¹,

Forma²,

Ciesielski³

et al. 2014

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IntroductionOvarian cancer is one of the most difficult problems in gynecologic oncology and the search for new drugs effective in the treatment of this kind of cancer, especially in cases resistant to current forms of therapy, remains a challenging priority.The aim of the studyThe aim of the study was to analyze the effect of metformin on apoptosis and the BIRC5 gene expression in ovarian cancer cell line SKOV-3. The BIRC5 gene encodes survivin protein.Material and methodsSKOV-3 cells were treated with metformin (10 mM). Apoptotic changes in studied cells were analyzed by double staining using a mixture of fluorochromes – Hoechst 33258/propidium iodide (PI). The expression of the BIRC5 gene at the mRNA level was analyzed using the real-time PCR technique.ResultsTreatment of cells with metformin causes changes in the cell shape from oval to spindle and leads to the separation of the cells from the monolayer. Furthermore, metformin induces apoptosis and necrosis of ovarian cancer cells. A statistically significant increase in the number of apoptotic cells after 48 and 72 hours’ treatment with metformin relative to a control cells seems to be correlated with a decrease in the expression of the BIRC5 gene at the mRNA level.ConclusionsMetformin seems to be a promising agent, whose use in ovarian cancer patients may contribute to improving the effectiveness of therapy.

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“…An alternative approach could be the use of pharmacological agents that preserve the mesothelium. With regard to ovarian cancer, hormone treatment with Tamoxifen is often used in conjunction with chemotherapy and other therapies [ 154 ]. Tamoxifen is a synthetic modulator of the estrogen receptor that is known to act in peritoneal tissue.…”

Section: Mesothelial-to-mesenchymal Transition As a Potential Thermentioning

confidence: 99%

The Mesothelial Origin of Carcinoma Associated-Fibroblasts in Peritoneal Metastasis

Rynne-Vidal¹,

Jiménez‐Heffernan²,

Fernández-Chacón³

et al. 2015

Cancers

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Solid tumors are complex and unstructured organs that, in addition to cancer cells, also contain other cell types. Carcinoma-associated fibroblasts (CAFs) represent an important population in the tumor microenviroment and participate in several stages of tumor progression, including cancer cell migration/invasion and metastasis. During peritoneal metastasis, cancer cells detach from the primary tumor, such as ovarian or gastrointestinal, disseminate through the peritoneal fluid and colonize the peritoneum. Tumor cells metastasize by attaching to and invading through the mesothelial cell (MC) monolayer that lines the peritoneal cavity, then colonizing the submesothelial compact zone where CAFs accumulate. CAFs may derive from different sources depending on the surrounding metastatic niche. In peritoneal metastasis, a sizeable subpopulation of CAFs originates from MCs through a mesothelial-to-mesenchymal transition (MMT), which promotes adhesion, invasion, vascularization and subsequent tumor growth. The bidirectional communication between cancer cells and MC-derived CAFs via secretion of a wide range of cytokines, growth factors and extracellular matrix components seems to be crucial for the establishment and progression of the metastasis in the peritoneum. This manuscript provides a comprehensive review of novel advances in understanding how peritoneal CAFs provide cancer cells with a supportive microenvironment, as well as the development of future therapeutic approaches by interfering with the MMT in the peritoneum.

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The role of hormonal factors and endocrine therapy in ovarian cancer

Cited by 7 publications

References 45 publications

An ovarian cancer model with positive ER: Reversion of ER antagonist resistance by Src blockade

An ovarian cancer model with positive ER: Reversion of ER antagonist resistance by Src blockade

Effect of metformin on apoptosis induction in ovarian cancer cells

The Mesothelial Origin of Carcinoma Associated-Fibroblasts in Peritoneal Metastasis

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