The expression and clinical significance of ERß/ERα in ovarian cancer: can we predict the effectiveness of platinum plus taxane therapy?

Estrogens play an extremely important role in regulating the proliferation of ovarian cancer. The estrogen receptor alpha (ERα) stimulates cell growth, whereas ERß can be attributed to tumor suppressors. The study aims to assess the relationship between the expression of estrogen receptors in tumors and the efficacy of front-line platinum plus taxane chemotherapy in ovarian cancer patients. MATERIALS AND METHODS: ERα and ERß tumor expression was evaluated quantitatively by flow cytometry in a narrowly defined group (31 patients): stage III high-grade serous ovarian carcinoma (HGSOC), suboptimal surgical cytoreduction, front-line platinum plus taxane chemotherapy (front-line, six cycles). RESULTS: The median of progression-free survival (PFS) was 2 times greater (18 vs 8 months, p = 0.04) and the recurrence risk (HR) was 2.2 times (95 % CI: 1.1-6.2, p = 0.04) lower in the group with high (in more than 40% of the cells) vs low level of ERß tumor expression. The statistically significant difference between PFS in the groups with high vs low tumor ERα expression was not revealed. CONCLUSION: A high level of ERß and not ERα expression can predict the efficacy of front-line platinum plus taxane chemotherapy in stage III HGSOC patients. The status of estrogen receptor beta can be considered as one of the possible predictors for evaluating the effectiveness of ovarian cancer therapy.

A new approach to epithelial-mesenchymal transition diagnostics in epithelial tumors: double immunofluorescent staining and flow cytometry.

A new method of double immunofluorescent staining for flow cytometry has been created to evaluate quantitative expression of mesenchymal protein vimentin only in epithelial cells of a solid tumor that is a mix of different origin cells. De novo vimentin expression is strongly associated with epithelial-mesenchymal transition and therefore is a metastatic potential marker of epithelial tumor cells. In comparison with semiquantitative available methods, the proposed one has several advantages, such as the accurate measurement of the marker's expression, and minimization of spatial and temporal tumor heterogeneity. Clinical validation of the method has revealed inverse correlation between the quantitative index of epithelial-mesenchymal transition level and progression-free survival using Kaplan-Meier curves and the COX proportional hazards ratio in 32 ovarian cancer patients.

Tamoxifen Never Ceases to Amaze: New Findings on Non-Estrogen Receptor Molecular Targets and Mediated Effects.

Tamoxifen is a first targeted drug that continues to be the gold standard in treatment of estrogen receptor positive breast cancer for almost 50 years. The current review is an update of the paper published in 2012. We provide the new data on the tamoxifen targets that are the key points of signaling cascades activating cellular proliferation, which determines aggressiveness of disease and chemotherapy resistance or sensitivity. Some inspiring clinical cases dealing with tamoxifen efficiency in treatment of different tumors are discussed. Additionally, the review includes data on antiviral, antibacterial, antifungal and antiparasitic activity of tamoxifen.

Tamoxifen non-estrogen receptor mediated molecular targets.

Recent experimental studies revealing new biological effects of tamoxifen on tumor cells both expressing and not expressing different types of estrogen receptors (ERα and ERß) show new aspects of a seemingly well known agent. This review describes tamoxifen targets, the blocking of which leads to inhibition of tumor cell growth and angiogenesis, stimulation of programmed cell death (apoptosis, autophagia and necrosis), inhibition of multidrug resistance, invasion and metastasis. Since outcomes of tamoxifen action on cells are prognostically good from the point of view of both tumor growth/metastasis inhibition and tumor response to drug therapy, the authors believe this is an extremely important addition to tamoxifen antiestrogenic effect. Arguments are provided to consider the strategy of long-term tamoxifen treatment proposed by Professor Craig V. Jordan in the 1970s that is also applicable to the treatment of other tumors. This is, first of all, the fact that expression of estrogen receptor-beta that can also be targeted by tamoxifen therapy in solid tumors of practically all known sites and histologies. The authors believe that molecular biological screening of patients with respect to expression of tamoxifen cellular targets other than ERα and ERß is needed to use to the full all tamoxifen biological activities other than modulation of estrogen receptors during long-term adjuvant therapy for cancers of various sites.