Folate receptor: a potential target in ovarian cancer

Pteridines ◽  
2015 ◽  
Vol 26 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Marie Bartouskova ◽  
Bohuslav Melichar ◽  
Beatrice Mohelnikova-Duchonova
Keyword(s):  
Ovarian Cancer ◽  
Anticancer Agents ◽  
Poor Prognosis ◽  
Current Knowledge ◽  
Folate Receptor ◽  
Gynecological Cancer ◽  
Predictive Biomarkers ◽  
Receptor Expression ◽  
Advanced Stage ◽  
Potential Therapeutic Target

AbstractOvarian cancer is the most frequent cause of gynecological cancer-related death. Unfortunately, many patients are diagnosed at an advanced stage and have a poor prognosis. The standard treatment for advanced disease involves maximal cytoreductive surgery and chemotherapy based on platinum compounds and taxanes. Patients presenting at an advanced stage have a higher risk of recurrence. The development of drug resistance currently represents a major obstacle in the systematic treatment and, therefore, the discovery of new anticancer agents and approaches should improve the poor prognosis of these patients. Folate receptor α is overexpressed in epithelial ovarian cancer (EOC), but has limited expression in nonmalignant human tissues. The degree of folate receptor expression corresponds with the stage and grade of the disease. Because of this, folate receptor α seems to be a potential therapeutic target for the treatment of ovarian cancer. Currently, several approaches have been studied to target this protein in ovarian cancer treatment. This review summarizes current knowledge about the potential usage of folate receptors as prognostic and predictive biomarkers as well as their role in the management and targeted therapy of ovarian cancer.

scholarly journals Prognostic significance of bone marrow FDG uptake in patients with gynecological cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kotaro Shimura ◽  
Seiji Mabuchi ◽  
Naoko Komura ◽  
Eriko Yokoi ◽  
Katsumi Kozasa ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Bone Marrow ◽  
Poor Prognosis ◽  
Gynecological Cancer ◽  
Prognostic Significance ◽  
Standardized Uptake Value ◽  
Suppressor Cells ◽  
Underlying Mechanism ◽  
Fdg Uptake

AbstractWe investigated the prognostic significance and the underlying mechanism of increased bone marrow (BM) 2-(18F) fluoro-2-deoxy-D-glucose as a tracer (FDG)-uptake in patients with gynecological cancer. A list of patients diagnosed with cervical, endometrial, and ovarian cancer from January 2008 to December 2014 were identified. Then, through chart reviews, 559 patients who underwent staging by FDG-positron emission tomography (PET)/computed tomography (CT) and subsequent surgical resection were identified, and their clinical data were reviewed retrospectively. BM FDG-uptake was evaluated using maximum standardized uptake value (SUVmax) and BM-to-aorta uptake ratio (BAR). As a result, we have found that increased BAR was observed in 20 (8.7%), 21 (13.0%), 21 (12.6%) of cervical, endometrial, and ovarian cancer, respectively, and was associated with significantly shorter survival. Increased BAR was also closely associated with increased granulopoiesis. In vitro and in vivo experiments revealed that tumor-derived granulocyte colony-stimulating factor (G-CSF) was involved in the underlying causative mechanism of increased BM FDG-uptake, and that immune suppression mediated by G-CSF-induced myeloid-derived suppressor cells (MDSCs) is responsible for the poor prognosis of this type of cancer. In conclusion, increased BM FDG-uptake, as represented by increased BAR, is an indicator of poor prognosis in patients with gynecological cancer.

scholarly journals Identification of FGFR4 as a Potential Therapeutic Target for Advanced-Stage, High-Grade Serous Ovarian Cancer

2013 ◽  
Vol 19 (4) ◽  
pp. 809-820 ◽  
Author(s):  
Tarrik M. Zaid ◽  
Tsz-Lun Yeung ◽  
Melissa S. Thompson ◽  
Cecilia S. Leung ◽  
Tom Harding ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Therapeutic Target ◽  
High Grade ◽  
Advanced Stage ◽  
Serous Ovarian Cancer ◽  
Potential Therapeutic Target

scholarly journals Notch3 Overexpression as Potential Therapeutic Target in Advanced Stage Chemoresistant Ovarian Cancer

2012 ◽  
Vol 138 (4) ◽  
pp. 535-544 ◽  
Author(s):  
Mohammed Tanjimur Rahman ◽  
Kentaro Nakayama ◽  
Munmun Rahman ◽  
Hiroshi Katagiri ◽  
Atsuko Katagiri ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Therapeutic Target ◽  
Advanced Stage ◽  
Potential Therapeutic Target ◽  
Chemoresistant Ovarian Cancer

A Phase I/II Study of Dose-Intense Paclitaxel with Cisplatin and Cyclophosphamide as Initial Therapy of Poor-Prognosis Advanced-Stage Epithelial Ovarian Cancer

1996 ◽  
Vol 62 (2) ◽  
pp. 181-191 ◽  
Author(s):  
Elise C. Kohn ◽  
Gisele A. Sarosy ◽  
Patricia Davis ◽  
Michaele Christian ◽  
Charles E. Link ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase I ◽  
Epithelial Ovarian Cancer ◽  
Poor Prognosis ◽  
Initial Therapy ◽  
Advanced Stage

scholarly journals Role of Circulating Biomarkers in Platinum-Resistant Ovarian Cancer

2021 ◽  
Vol 22 (24) ◽  
pp. 13650
Author(s):  
Carolina Maria Sassu ◽  
Innocenza Palaia ◽  
Serena Maria Boccia ◽  
Giuseppe Caruso ◽  
Giorgia Perniola ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Poor Prognosis ◽  
Gynecological Cancer ◽  
Circulating Biomarkers ◽  
Tumor Biopsy ◽  
Non Invasive ◽  
The Poor ◽  
Platinum Resistant ◽  
New Biomarkers

Ovarian cancer (OC) is the second most common cause of death in women with gynecological cancer. Considering the poor prognosis, particularly in the case of platinum-resistant (PtR) disease, a huge effort was made to define new biomarkers able to help physicians in approaching and treating these challenging patients. Currently, most data can be obtained from tumor biopsy samples, but this is not always available and implies a surgical procedure. On the other hand, circulating biomarkers are detected with non-invasive methods, although this might require expensive techniques. Given the fervent hope in their value, here we focused on the most studied circulating biomarkers that could play a role in PtR OC.

scholarly journals Thy-1 predicts poor prognosis and is associated with self-renewal in ovarian cancer

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Elizabeth V. Connor ◽  
Caner Saygin ◽  
Chad Braley ◽  
Andrew C. Wiechert ◽  
Sheelarani Karunanithi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Stem Cell ◽  
In Situ Hybridization ◽  
Poor Prognosis ◽  
Proliferative Capacity ◽  
Potential Therapeutic Target ◽  
Self Renewal ◽  
Ovarian Cancers ◽  
Rna In Situ Hybridization

Abstract Background Ovarian cancer is the leading cause of gynecologic cancer death in the United States despite effective first-line systemic chemotherapy. Cancer stem cells (CSCs) retain the ability to self-renew and proliferate and may be a means of harboring disease that evades standard treatment strategies. We previously performed a high-throughput screen to assess differential protein expression in ovarian CSCs compared to non-CSCs and observed that Thy-1 was more highly expressed in CSCs. Our primary aim was to validate Thy-1 (CD90) as a cancer stem cell (CSC) marker in epithelial ovarian cancer (EOC), correlate with clinical outcomes, and assess as a potential therapeutic target. Results Kaplan Meier (KM) Plotter data were correlated with survival outcomes. Quantitative real-time PCR, flow cytometry, and immunoblots assessed RNA and protein expression. Limiting dilution assays assessed self-renewal capacity and proliferation assays assessed proliferative capacity. RNA in-situ hybridization was performed on patient specimens to assess feasibility. Thy-1 (CD90) is more highly expressed in ovarian CSCs than non-CSCs, in EOC compared to benign ovarian epithelium (P < 0.001), and is highest in serous EOC (P < 0.05). Serous ovarian cancers with high Thy-1 expression have poorer outcomes (median PFS 15.8 vs. 18.3 months, P = 0 < 0.001; median OS 40.1 v. 45.8 months, P = 0.036). Endometrioid ovarian cancers with high Thy-1 have poorer PFS, but no difference in OS (upper quartile PFS 34 v. 11 months, P = 0.013; quartile OS not reached, P = 0.69). In vitro, Thy-1 expression is higher in CSCs versus non-CSCs. EOC cells with high Thy-1 expression demonstrate increased proliferation and self-renewal. Thy-1 knockdown in EOC cells decreases proliferative capacity and self-renewal capacity, and knockdown is associated with decreased expression of stem cell transcription factors NANOG and SOX2. RNA in situ hybridization is feasible in ovarian cancer tissue specimens. Conclusions Thy-1 is a marker of ovarian CSCs. Increased expression of Thy-1 in EOC predicts poor prognosis and is associated with increased proliferative and self-renewal capacity. Thy-1 knockdown decreases proliferative and self-renewal capacity, and represents a potential therapeutic target.

scholarly journals Ten-year follow-up of a phase 2 study of dose-intense paclitaxel with cisplatin and cyclophosphamide as initial therapy for poor-prognosis, advanced-stage epithelial ovarian cancer

Cancer ◽  
2010 ◽  
Vol 116 (6) ◽  
pp. 1476-1484 ◽  
Author(s):  
Gisele A. Sarosy ◽  
Mahrukh M. Hussain ◽  
Michael V. Seiden ◽  
Arlan F. Fuller ◽  
Najmosama Nikrui ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Poor Prognosis ◽  
Initial Therapy ◽  
Advanced Stage ◽  
Phase 2 ◽  
Phase 2 Study

Expression Profiles of Genes Involved in Poor Prognosis of Epithelial Ovarian Carcinoma: A Review

2009 ◽  
Vol 19 (6) ◽  
pp. 992-997 ◽  
Author(s):  
Shozo Yoshida ◽  
Naoto Furukawa ◽  
Shoji Haruta ◽  
Yasuhito Tanase ◽  
Seiji Kanayama ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Poor Prognosis ◽  
Epithelial Mesenchymal Transition ◽  
Expression Profiles ◽  
Gynecological Cancer ◽  
Cancer Prognosis ◽  
Specific Expression ◽  
Mesenchymal Transition ◽  
Wide Range

Background:Epithelial ovarian cancer (EOC) is the commonest cause of gynecological cancer-related mortality. Although the prognosis for patients with advanced cancer is poor, there is a wide range of outcomes for individual patients.Objective:The aim of this study was to review molecular factors predictive of poor prognosis of women with EOC by reviewing microarray research identifying gene expression profiles.Methods:A systematic search was performed in the electronic databases PubMed and ScienceDirect up to July 2008, combining the keywords "genome-wide," "microarray," "epithelial ovarian cancer" "prognosis," and "epithelial-mesenchymal transition" with specific expression profiles of genes.Results:Many genes that participated in cell signaling, growth factors, transcription factors, proteinases, metabolism, cell adhesion, extracellular matrix component, cell proliferation, and anti-apoptosis were overexpressed in patients with poor prognosis. Several important prognosis-related genes overlap with those known to be regulated by epithelial-mesenchymal transition (EMT). This signaling pathway of EMT (E-cadherin, β-catenin, receptor tyrosine kinases, NF-κB, TGF-β, or Wnt signalings) will be discussed, as it provides new insights into a new treatment strategy.Conclusions:This review summarizes recent advances in prognosis-related molecular biology. Collectively, molecular changes possibly through EMT are considered to be a major contributor to the poor prognosis of EOC.

scholarly journals Epigenetic silencing of BLU through interfering apoptosis results in chemoresistance and poor prognosis of ovarian serous carcinoma patients

2013 ◽  
Vol 20 (2) ◽  
pp. 213-227 ◽  
Author(s):  
Ying-Cheng Chiang ◽  
Ming-Cheng Chang ◽  
Pao-Jen Chen ◽  
Meei-Maan Wu ◽  
Chang-Yao Hsieh ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Multivariate Analysis ◽  
Poor Prognosis ◽  
Methylation Status ◽  
Progression Free Survival ◽  
Serous Carcinoma ◽  
Ovarian Cancer Cells ◽  
Advanced Stage ◽  
Ovarian Serous Carcinoma

Epithelial ovarian carcinoma is usually present at the advanced stage, during which the patients generally have poor prognosis. Our study aimed to evaluate the correlation of gene methylation and the clinical outcome of patients with advanced-stage, high-grade ovarian serous carcinoma. The methylation status of eight candidate genes was first evaluated by methylation-specific PCR and capillary electrophoresis to select three potential genes including DAPK, CDH1, and BLU (ZMYND10) from the exercise group of 40 patients. The methylation status of these three genes was further investigated in the validation group consisting of 136 patients. Patients with methylated BLU had significantly shorter progression-free survival (PFS; hazard ratio (HR) 1.48, 95% CI 1.01–2.56, P=0.013) and overall survival (OS; HR 1.83, 95% CI 1.07–3.11, P=0.027) in the multivariate analysis. Methylation of BLU was also an independent risk factor for 58 patients undergoing optimal debulking surgery for PFS (HR 2.37, 95% CI 1.03–5.42, P=0.043) and OS (HR 3.96, 95% CI 1.45–10.81, P=0.007) in the multivariate analysis. A possible mechanism of BLU in chemoresistance was investigated in ovarian cancer cell lines by in vitro apoptotic assays. In vitro studies have shown that BLU could upregulate the expression of BAX and enhance the effect of paclitaxel-induced apoptosis in ovarian cancer cells. Our study suggested that methylation of BLU could be a potential prognostic biomarker for advanced ovarian serous carcinoma.

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