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New Insights into Endometrial Cancer 2023

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (25 December 2023) | Viewed by 2099

Special Issue Editor

Special Issue Information

Dear Colleagues,

Endometrial Cancer is a hormone dependent cancer with an increasing incidence that is estimated to grow in the next years. It is typically treated with surgery and/or chemo/radiation therapy. Recently, it has been demonstrated the clinical benefit of hormone therapies for advanced and recurrent Endometrial Cancers underlined the need to examine their characteristics (particularly steroid hormone receptors expression and functions) to assess their better use. Furthermore, a critical phase to drive the clinicians in the therapeutic choice is the histopathological and molecular classification. In fact, an even current challenge is to integrate IHC markers with molecular tests to identify prognostic groups. Moreover, the observations of the immunosuppressive nature of the endometrial cancer environment are leading to promote studies to assess therapies aimed to boost immune response that might represent a significant potential in the disease treatment. For this reason, current and ongoing studies are trying to improve clinical responses through immunotherapies strategies combined or not with classic treatments.

This open-access Special Issue will bring together original research and review articles on molecular oncology with attention to endometrial cancer. It highlights new findings, methods, and technical advances in molecular cancer research. The main feature of this Special Issue is to provide an open-source sharing of significant works in the field of molecular oncology that can increase our understanding of endometrial cancer development, which may lead to the discovery of new molecular diagnostic technologies and targeted therapeutics.

Topics include but are not limited to:

  • Molecular methods to personalize endometrial cancer screening and detection;
  • Identification and new aspects of cellular signaling molecules and pathways for target discovery, drug design, personalized and gender medicine;
  • DDI discovery in endometrial cancer management;
  • Drug repurposing for endometrial cancer prevention/treatment;
  • Molecular modeling studies.

Dr. Laura Paleari
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Published Papers (2 papers)

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Research

20 pages, 6178 KiB  
Article
Rel Family Transcription Factor NFAT5 Upregulates COX2 via HIF-1α Activity in Ishikawa and HEC1a Cells
by Toshiyuki Okumura, Janet P. Raja Xavier, Jana Pasternak, Zhiqi Yang, Cao Hang, Bakhtiyor Nosirov, Yogesh Singh, Jakob Admard, Sara Y. Brucker, Stefan Kommoss, Satoru Takeda, Annette Staebler, Florian Lang and Madhuri S. Salker
Int. J. Mol. Sci. 2024, 25(7), 3666; https://doi.org/10.3390/ijms25073666 - 25 Mar 2024
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Abstract
Nuclear factor of activated T cells 5 (NFAT5) and cyclooxygenase 2 (COX2; PTGS2) both participate in diverse pathologies including cancer progression. However, the biological role of the NFAT5-COX2 signaling pathway in human endometrial cancer has remained elusive. The present study explored whether [...] Read more.
Nuclear factor of activated T cells 5 (NFAT5) and cyclooxygenase 2 (COX2; PTGS2) both participate in diverse pathologies including cancer progression. However, the biological role of the NFAT5-COX2 signaling pathway in human endometrial cancer has remained elusive. The present study explored whether NFAT5 is expressed in endometrial tumors and if NFAT5 participates in cancer progression. To gain insights into the underlying mechanisms, NFAT5 protein abundance in endometrial cancer tissue was visualized by immunohistochemistry and endometrial cancer cells (Ishikawa and HEC1a) were transfected with NFAT5 or with an empty plasmid. As a result, NFAT5 expression is more abundant in high-grade than in low-grade endometrial cancer tissue. RNA sequencing analysis of NFAT5 overexpression in Ishikawa cells upregulated 37 genes and downregulated 20 genes. Genes affected included cyclooxygenase 2 and hypoxia inducible factor 1α (HIF1A). NFAT5 transfection and/or treatment with HIF-1α stabilizer exerted a strong stimulating effect on HIF-1α promoter activity as well as COX2 expression level and prostaglandin E2 receptor (PGE2) levels. Our findings suggest that activation of NFAT5—HIF-1α—COX2 axis could promote endometrial cancer progression. Full article
(This article belongs to the Special Issue New Insights into Endometrial Cancer 2023)
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13 pages, 3539 KiB  
Article
EphA2- and HDAC-Targeted Combination Therapy in Endometrial Cancer
by Robiya Joseph, Santosh K. Dasari, Sujanitha Umamaheswaran, Lingegowda S. Mangala, Emine Bayraktar, Cristian Rodriguez-Aguayo, Yutuan Wu, Nghi Nguyen, Reid T. Powell, Mary Sobieski, Yuan Liu, Mark Seungwook Kim, Sara Corvigno, Katherine Foster, Pahul Hanjra, Thanh Chung Vu, Mamur A. Chowdhury, Paola Amero, Clifford Stephan, Gabriel Lopez-Berestein, Shannon N. Westin and Anil K. Soodadd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2024, 25(2), 1278; https://doi.org/10.3390/ijms25021278 - 20 Jan 2024
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Abstract
Endometrial cancer is the most frequent malignant tumor of the female reproductive tract but lacks effective therapy. EphA2, a receptor tyrosine kinase, is overexpressed by various cancers including endometrial cancer and is associated with poor clinical outcomes. In preclinical models, EphA2-targeted drugs had [...] Read more.
Endometrial cancer is the most frequent malignant tumor of the female reproductive tract but lacks effective therapy. EphA2, a receptor tyrosine kinase, is overexpressed by various cancers including endometrial cancer and is associated with poor clinical outcomes. In preclinical models, EphA2-targeted drugs had modest efficacy. To discover potential synergistic partners for EphA2-targeted drugs, we performed a high-throughput drug screen and identified panobinostat, a histone deacetylase inhibitor, as a candidate. We hypothesized that combination therapy with an EphA2 inhibitor and panobinostat leads to synergistic cell death. Indeed, we found that the combination enhanced DNA damage, increased apoptosis, and decreased clonogenic survival in Ishikawa and Hec1A endometrial cancer cells and significantly reduced tumor burden in mouse models of endometrial carcinoma. Upon RNA sequencing, the combination was associated with downregulation of cell survival pathways, including senescence, cyclins, and cell cycle regulators. The Axl-PI3K-Akt-mTOR pathway was also decreased by combination therapy. Together, our results highlight EphA2 and histone deacetylase as promising therapeutic targets for endometrial cancer. Full article
(This article belongs to the Special Issue New Insights into Endometrial Cancer 2023)
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