Wise Management of Ovarian Cancer: On the Cutting Edge
Stergios Boussios,Christos Mikropoulos,Eleftherios P. Samartzis,Peeter Karihtala,Michele Moschetta,Matin Sheriff,Afroditi Karathanasi,Agne Sadauskaite,Elie El Rassy,Nicholas Pavlidis +9 more
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TLDR
An overview of the main aspects of ovarian cancer, catapulted from the molecular mechanisms to therapeutic considerations is offered.Abstract:
Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer mortality among women. Two-thirds of patients present at advanced stage at diagnosis, and the estimated 5 year survival rate is 20–40%. This heterogeneous group of malignancies has distinguishable etiology and molecular biology. Initially, single-gene sequencing was performed to identify germline DNA variations associated with EOC. However, hereditary EOC syndrome can be explained by germline pathogenic variants (gPVs) in several genes. In this regard, next-generation sequencing (NGS) changed clinical diagnostic testing, allowing assessment of multiple genes simultaneously in a faster and cheaper manner than sequential single gene analysis. As we move into the era of personalized medicine, there is evidence that poly (ADP-ribose) polymerase (PARP) inhibitors exploit homologous recombination (HR) deficiency, especially in breast cancer gene 1 and 2 (BRCA1/2) mutation carriers. Furthermore, extensive preclinical data supported the development of aurora kinase (AURK) inhibitors in specific tumor types, including EOC. Their efficacy may be optimized in combination with chemotherapeutic or other molecular agents. The efficacy of metformin in ovarian cancer prevention is under investigation. Certain mutations, such as ARID1A mutations, and alterations in the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway, which are specific in ovarian clear cell carcinoma (OCCC) and endometrioid ovarian carcinoma (EnOC), may offer additional therapeutic targets in these clinical entities. Malignant ovarian germ cell tumors (MOGCTs) are rare and randomized trials are extremely challenging for the improvement of the existing management and development of novel strategies. This review attempts to offer an overview of the main aspects of ovarian cancer, catapulted from the molecular mechanisms to therapeutic considerations.read more
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Journal ArticleDOI
BRCA Mutations in Ovarian and Prostate Cancer: Bench to Bedside
Stergios Boussios,Elie El Rassy,Michele Moschetta,Aruni Ghose,Sola Adeleke,Elisabet Sánchez,Matin Sheriff,Cyrus Chargari,Nicholas Pavlidis +8 more
TL;DR: The mechanisms of DDR, the potential for genomic analysis of ovarian and prostate cancer, and therapeutics of PARP inhibitors, along with predictive biomarkers are explored, with a major concern regarding the need to identify reliable biomarkers predictive of treatment response.
Journal ArticleDOI
Applications of Proteomics in Ovarian Cancer: Dawn of a New Era
Aruni Ghose,Srikar Gullapalli,Naila Chohan,Anita Bolina,Michele Moschetta,Elie El Rassy,Stergios Boussios +6 more
TL;DR: There is an urgent need to better understand how the genomic and epigenomic heterogeneity intrinsic to OC is reflected at the protein level, and how this information could potentially lead to prolonged survival.
Journal ArticleDOI
Aberrations of DNA repair pathways in prostate cancer: a cornerstone of precision oncology.
Stergios Boussios,Elie El Rassy,Sidrah Shah,Evangelia Ioannidou,Matin Sheriff,Nicholas Pavlidis +5 more
TL;DR: Prostate cancer is the second most commonly diagnosed malignancy and the fifth most frequent cause of cancer-related death in males worldwide [1] as mentioned in this paper, and it is the most common cause of prostate cancer related death in men.
Journal ArticleDOI
Angiogenesis and Anti-Angiogenic Treatment in Prostate Cancer: Mechanisms of Action and Molecular Targets
Evangelia Ioannidou,Michele Moschetta,Sidrah Shah,Jack Steven Parker,Mehmet Akif Ozturk,George Pappas-Gogos,Matin Sheriff,Elie El Rassy,Stergios Boussios +8 more
TL;DR: In this article, a comprehensive review of the pathways involved in the angiogenesis, the chemotherapeutic agents with antiangiogenic activity, the available studies on antiagiogenic agents and the potential mechanisms of resistance is presented.
Journal ArticleDOI
Non-Epithelial Ovarian Cancers: How Much Do We Really Know?
Alison Cheung,Sidrah Shah,Jack Parker,Pavandeep Soor,Anu Limbu,Matin Sheriff,Stergios Boussios +6 more
TL;DR: An update on the clinical presentation, pathology, genetics, treatment and survival of the main histological subtypes of the GCT and the SCST, as well as of ovarian small cell carcinomas is provided.
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Journal ArticleDOI
ARID1A mutations in endometriosis-associated ovarian carcinomas.
Kimberly C. Wiegand,Sohrab P. Shah,Osama M. Al-Agha,Yongjun Zhao,Kane Tse,Thomas Zeng,Janine Senz,Melissa K. McConechy,Michael S. Anglesio,Steve E. Kalloger,Winnie Yang,Alireza Heravi-Moussavi,Ryan Giuliany,Christine Chow,John Fee,Abdalnasser Zayed,Leah M Prentice,Nataliya Melnyk,Gulisa Turashvili,Allen Delaney,Jason Madore,Stephen Yip,Andrew McPherson,Gavin Ha,Lynda Bell,Sian Fereday,Angela Tam,Laura Galletta,Patricia N. Tonin,Diane Provencher,Dianne Miller,Steven J.M. Jones,Richard A. Moore,Gregg B. Morin,Gregg B. Morin,Arusha Oloumi,Niki Boyd,Samuel Aparicio,Ie Ming Shih,Anne Marie Mes-Masson,David D.L. Bowtell,David D.L. Bowtell,Martin Hirst,Blake Gilks,Marco A. Marra,Marco A. Marra,David G. Huntsman +46 more
TL;DR: These data implicate ARID1A as a tumor-suppressor gene frequently disrupted in ovarian clear-cell and endometrioid carcinomas.
Journal ArticleDOI
Olaparib Monotherapy in Patients With Advanced Cancer and a Germline BRCA1/2 Mutation
Bella Kaufman,Ronnie Shapira-Frommer,Rita K. Schmutzler,M. William Audeh,Michael Friedlander,Judith Balmaña,Gillian Mitchell,Georgeta Fried,Salomon M. Stemmer,Ayala Hubert,Ora Rosengarten,Mariana Steiner,Niklas Loman,Karin Bowen,Anitra Fielding,Susan M. Domchek +15 more
TL;DR: Responses to olaparib were observed across different tumor types associated with germline BRCA1/2 mutations, and warrants further investigation in confirmatory studies.
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