Ovarian Cancer Pathogenesis: A Model in Evolution
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TLDR
An overview of the current models of ovarian cancer pathogenesis is provided, highlighting recent findings implicating the fallopian tube fimbria as a possible site of origin of ovarian carcinomas.Abstract:
Ovarian cancer is a deadly disease for which there is no effective means of early detection. Ovarian carcinomas comprise a diverse group of neoplasms, exhibiting a wide range of morphological characteristics, clinical manifestations, genetic alterations, and tumor behaviors. This high degree of heterogeneity presents a major clinical challenge in both diagnosing and treating ovarian cancer. Furthermore, the early events leading to ovarian carcinoma development are poorly understood, thus complicating efforts to develop screening modalities for this disease. Here, we provide an overview of the current models of ovarian cancer pathogenesis, highlighting recent findings implicating the fallopian tube fimbria as a possible site of origin of ovarian carcinomas. The ovarian cancer model will continue to evolve as we learn more about the genetics and etiology of this disease.read more
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Journal ArticleDOI
Epithelial Ovarian Cancer
TL;DR: Urgent progress is needed to develop evidence and consensus-based treatment guidelines for each subgroup, and requires close international cooperation in conducting clinical trials through academic research groups such as the Gynecologic Cancer Intergroup.
Journal ArticleDOI
High grade serous ovarian carcinomas originate in the fallopian tube
S. Intidhar Labidi-Galy,S. Intidhar Labidi-Galy,Eniko Papp,Dorothy Hallberg,Noushin Niknafs,Noushin Niknafs,Vilmos Adleff,Michaël Noë,Rohit Bhattacharya,Rohit Bhattacharya,Marian Novak,Siân Jones,Jillian Phallen,Carolyn Hruban,Michelle S. Hirsch,Douglas I. Lin,Douglas I. Lin,Lauren E. Schwartz,Cecile L. Maire,Jean-Christophe Tille,Michaela Bowden,Ayse Ayhan,Laura D. Wood,Robert B. Scharpf,Robert J. Kurman,Tian Li Wang,Ie Ming Shih,Rachel Karchin,Rachel Karchin,Ronny Drapkin,Ronny Drapkin,Ronny Drapkin,Victor E. Velculescu +32 more
TL;DR: Genetic aberrances in fallopian tube lesions, ovarian cancers, and metastases from HGSOC patients are analyzed and evolutionary analyses reveal that p53 signatures and STICs are precursors of ovarian carcinoma and identify a window of 7 years between development of a STIC and initiation of ovarian cancer, with metastases following rapidly thereafter.
Journal ArticleDOI
A comprehensive analysis of PAX8 expression in human epithelial tumors.
Anna Laury,Ruth Perets,Huiying Piao,Jeffrey F. Krane,Justine A. Barletta,Christopher A. French,Lucian R. Chirieac,Rosina T. Lis,Massimo Loda,Jason L. Hornick,Ronny Drapkin,Michelle S. Hirsch +11 more
TL;DR: Results show that PAX8 is a highly sensitive marker for thyroid, renal, Müllerian, and thymic tumors, and is an excellent marker for confirming primary tumor site.
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Modeling high-grade serous ovarian carcinogenesis from the fallopian tube
TL;DR: A system for studying human fallopian tube secretory epithelial cell (FTSEC) transformation is developed and it is shown that FTSECs immortalized with human telomerase reverse transcriptase plus SV40 large T and small T antigens are transformed by either oncogenic Ras (H-RasV12) or c-Myc expression, leading to increased proliferation, clonogenicity, and anchorage-independent growth.
Journal ArticleDOI
Iron addiction: a novel therapeutic target in ovarian cancer
Debargha Basuli,Lia Tesfay,Zhiyong Deng,Bibbin T. Paul,Yusuke Yamamoto,Gang Ning,Wa Xian,Frank McKeon,Miranda L. Lynch,Christopher P. Crum,Poornima Hegde,Molly Brewer,Xiaohong Wang,Lance D. Miller,Nathaniel A. Dyment,Frank M. Torti,Suzy V. Torti +16 more
TL;DR: The iron dependence of ovarian cancer TICs renders them exquisitely sensitive in vivo to agents that induce iron-dependent cell death (ferroptosis) as well as iron chelators, and thus creates a metabolic vulnerability that can be exploited therapeutically.
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