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

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.

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Cyclin E as a potential therapeutic target in high grade serous ovarian cancer

Gynecologic Oncology ◽

10.1016/j.ygyno.2016.07.111 ◽

2016 ◽

Vol 143 (1) ◽

pp. 152-158 ◽

Cited By ~ 40

Author(s):

J. Kanska ◽

M. Zakhour ◽

B. Taylor-Harding ◽

B.Y. Karlan ◽

W.R. Wiedemeyer

Keyword(s):

Ovarian Cancer ◽

Therapeutic Target ◽

Cyclin E ◽

High Grade ◽

Serous Ovarian Cancer ◽

Potential Therapeutic Target

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Genetic Association of Interleukin-31 Gene Polymorphisms with Epithelial Ovarian Cancer in Chinese Population

Disease Markers ◽

10.1155/2018/3503858 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Chenlu Liu ◽

Yanyun Wang ◽

Huizi Song ◽

Qin Li ◽

Yan Zhang ◽

...

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Therapeutic Target ◽

Gene Polymorphisms ◽

Chinese Population ◽

Clinical Characteristics ◽

Chinese Women ◽

Healthy Individuals ◽

Potential Therapeutic Target ◽

Kaplan Meier

Roles of interleukin-31 (IL-31) in the development and progression of human epithelial ovarian cancer are largely unknown. Studies report that the polymorphisms, rs7977932 C>G and rs4758680 C>A in IL-31, affect the expression level of IL-31. In the present study, we examined 412 patients with epithelial ovarian cancer and 428 healthy individuals to explore whether these polymorphisms are associated with the epithelial ovarian cancer in Chinese women. The genotype of the polymorphisms in each individual was identified. The associations of the polymorphisms with patients’ clinical characteristics and outcomes were evaluated. For rs7977932, the frequency of the CG/GG was significantly decreased in patients with epithelial ovarian cancer. However, the frequency of the rs4758680 CA/AA was significantly increased in those patients. Moreover, the frequency of rs7977932 CG/GG genotype was significantly higher in patients with less advanced FIGO stages. Kaplan-Meier curve showed that patients with CG/GG genotypes of rs7977932 had a decreased risk for recurrence compared to those with CC genotype. Our findings suggested that rs7977932 and rs4758680 of IL-31 may be associated with the development and progression of the epithelial ovarian cancer in the Chinese population. IL-31, therefore, may be a potential therapeutic target for the development of drugs to treat the disease.

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Abstract 799: Global genomic analysis identified PRKCI as a potential therapeutic target gene for human clear cell ovarian cancer.

10.1158/1538-7445.am2013-799 ◽

2013 ◽

Author(s):

Tsun Yee Tsang ◽

Gayatry Mohapatra ◽

Hiroaki Itamochi ◽

Samuel C. Mok ◽

Michael J. Birrer

Keyword(s):

Ovarian Cancer ◽

Therapeutic Target ◽

Target Gene ◽

Clear Cell ◽

Genomic Analysis ◽

Potential Therapeutic Target

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Gene amplificationCCNE1is related to poor survival and potential therapeutic target in ovarian cancer

Cancer ◽

10.1002/cncr.24987 ◽

2010 ◽

pp. NA-NA ◽

Cited By ~ 13

Author(s):

Naomi Nakayama ◽

Kentaro Nakayama ◽

Yeasmin Shamima ◽

Masako Ishikawa ◽

Atsuko Katagiri ◽

...

Keyword(s):

Ovarian Cancer ◽

Therapeutic Target ◽

Poor Survival ◽

Potential Therapeutic Target

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Krupple-Like Factor 5 is a Potential Therapeutic Target and Prognostic Marker in Epithelial Ovarian Cancer

Frontiers in Pharmacology ◽

10.3389/fphar.2020.598880 ◽

2020 ◽

Vol 11 ◽

Author(s):

Abdul K. Siraj ◽

Poyil Pratheeshkumar ◽

Sasidharan Padmaja Divya ◽

Sandeep Kumar Parvathareddy ◽

Khadija A. Alobaisi ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Growth ◽

Epithelial Ovarian Cancer ◽

Signaling Pathway ◽

Cell Lines ◽

Therapeutic Target ◽

Potential Therapeutic Target ◽

Mesenchymal Transition ◽

Stat3 Signaling ◽

Stat3 Signaling Pathway

Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy. Despite current therapeutic and surgical options, advanced EOC shows poor prognosis. Identifying novel molecular therapeutic targets is highly needed in the management of EOC. Krupple-like factor 5 (KLF5), a zinc-finger transcriptional factor, is highly expressed in a variety of cancer types. However, its role and expression in EOC is not fully illustrated. Immunohistochemical analysis was performed to assess KLF5 protein expression in 425 primary EOC samples using tissue microarray. We also addressed the function of KLF5 in EOC and its interaction with signal transducer and activator of transcription 3 (STAT3) signaling pathway. We found that KLF5 overexpressed in 53% (229/425) of EOC samples, and is associated with aggressive markers. Forced expression of KLF5 enhanced cell growth in low expressing EOC cell line, MDAH2774. Conversely, knockdown of KLF5 reduced cell growth, migration, invasion and progression of epithelial to mesenchymal transition in KLF5 expressing cell lines, OVISE and OVSAHO. Importantly, silencing of KLF5 decreased the self-renewal ability of spheroids generated from OVISE and OVSAHO cell lines. In addition, downregulation of KLF5 potentiated the effect of cisplatin to induce apoptosis in these cell lines. These data reveals the pro-tumorigenic role of KLF5 in EOC and uncover its role in activation of STAT3 signaling pathway, suggesting the importance of KLF5 as a potential therapeutic target for EOC therapy.

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MicroRNA-204-5p Inhibits Ovarian Cancer Cell Proliferation by Down-Regulating USP47

Cell Transplantation ◽

10.1177/0963689719877372 ◽

2019 ◽

Vol 28 (1_suppl) ◽

pp. 51S-58S ◽

Cited By ~ 7

Author(s):

Liangliang Hu ◽

Helena Kolibaba ◽

Siyou Zhang ◽

Minhua Cao ◽

Huihui Niu ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Therapeutic Target ◽

Molecular Mechanisms ◽

Ovarian Cancer Cell ◽

Malignant Tumors ◽

Gynecologic Cancer ◽

Cancer Cell Proliferation ◽

Potential Therapeutic Target ◽

Human Malignant Tumors

Ovarian cancer (OC) is the most lethal gynecologic cancer, and the incidence of OC has risen steadily worldwide. Numerous microRNAs (miRNAs) have been found to be involved in the progression of OC. miR-204-5p is down-regulated and functions as a tumor suppressor in various types of human malignant tumors. However, the biological roles and molecular mechanisms of miR-204-5p in OC still remain unclear. In this study, the aberrant down-regulation of miR-204-5p was detected in OC tissues. We also observed that miR-204-5p overexpression represses OC cell proliferation. Ubiquitin-specific peptidase 47 (USP47) is verified as the functional target of miR-204-5p, through which it plays an important biological role in OC. Our results uncover new functions and mechanisms for miR-204-5p in the progression of OC, and provide a potential therapeutic target for the treatment of OC.

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