scholarly journals Patient-derived cell line models revealed therapeutic targets and molecular mechanisms underlying disease progression of high grade serous ovarian cancer

2019 ◽  
Vol 459 ◽  
pp. 1-12 ◽  
Author(s):  
Caroline Kreuzinger ◽  
Isabel von der Decken ◽  
Andrea Wolf ◽  
Magdalena Gamperl ◽  
Julia Koller ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Disease Progression ◽  
Cell Line ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
Underlying Disease ◽  
High Grade ◽  
Serous Ovarian Cancer

scholarly journals Altered expression of different GalNAc-transferases is associated with disease progression and poor prognosis in women with high-grade serous ovarian cancer

2017 ◽  
Vol 51 (6) ◽  
pp. 1887-1897 ◽  
Author(s):  
Razan Sheta ◽  
Magdalena Bachvarova ◽  
Marie Plante ◽  
Jean Gregoire ◽  
Marie-Claude Renaud ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Disease Progression ◽  
Poor Prognosis ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Altered Expression

scholarly journals Genomics and molecular mechanisms of high grade serous ovarian cancer: the 12th Biennial Rivkin Center Ovarian Cancer Research Symposium

2019 ◽  
Vol 29 (Suppl 2) ◽  
pp. s7-s11
Author(s):  
Erinn B Rankin
Keyword(s):  
Ovarian Cancer ◽  
Cancer Research ◽  
Dna Repair ◽  
Molecular Mechanisms ◽  
New Technologies ◽  
Serous Carcinoma ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Poster Presentations ◽  
Oral Presentations

ObjectiveThe aim of this study was to review current research efforts in genomics and molecular mechanisms of high grade serous ovarian cancer, presented at the 12th Biennial Rivkin Center Ovarian Cancer Research Symposium, held at the University of Washington.MethodsThe 12th Biennial Rivkin Center Ovarian Cancer Research Symposium brought together leaders in the field to discuss recent advances in ovarian cancer research and therapy.ResultsThe genomics and molecular mechanisms of ovarian cancer session featured invited speaker presentations by Dr Alan D’ Andrea on ‘Deoxyribonucleic acid (DNA) repair in ovarian cancer’ and Dr Kathleen Cho on ‘Modeling the genomics of high grade serous carcinoma in the mouse’. Eight additional oral presentations and 46 poster presentations were selected from the submitted abstracts that highlighted current research efforts in p53, DNA repair, genomic instability and modeling disease in mice, and organoids in high grade serous ovarian cancer.ConclusionsNew technologies utilizing clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9 (CAS9) approaches in mice, organoids, and cell based screens continue to advance our knowledge of key molecular drivers of ovarian cancer initiation, progression, and drug resistance. Improved understanding of the mechanisms of poly ADP ribose polymerase inhibitor resistance may lead to new therapeutic strategies to enhance outcomes in women with high grade serous ovarian cancer.

scholarly journals PARP Inhibitors Display Differential Efficacy in Models of BRCA Mutant High-Grade Serous Ovarian Cancer

2021 ◽  
Vol 22 (16) ◽  
pp. 8506
Author(s):  
Kristie-Ann Dickson ◽  
Tao Xie ◽  
Christian Evenhuis ◽  
Yue Ma ◽  
Deborah J. Marsh
Keyword(s):  
Ovarian Cancer ◽  
Cell Line ◽  
Ovarian Cancer Cell Line ◽  
Acquired Resistance ◽  
Parp Inhibitors ◽  
Ovarian Cancer Cells ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Cancer Genes ◽  
Chemical Structures

Several poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors are now in clinical use for tumours with defects in BReast CAncer genes BRCA1 or BRCA2 that result in deficient homologous recombination repair (HRR). Use of olaparib, niraparib or rucaparib for the treatment of high-grade serous ovarian cancer, including in the maintenance setting, has extended both progression free and overall survival for women with this malignancy. While different PARP inhibitors (PARPis) are mechanistically similar, differences are apparent in their chemical structures, toxicity profiles, PARP trapping abilities and polypharmacological landscapes. We have treated ovarian cancer cell line models of known BRCA status, including the paired cell lines PEO1 and PEO4, and UWB1.289 and UWB1.289+BRCA1, with five PARPis (olaparib, niraparib, rucaparib, talazoparib and veliparib) and observed differences between PARPis in both cell viability and cell survival. A cell line model of acquired resistance to veliparib showed increased resistance to the other four PARPis tested, suggesting that acquired resistance to one PARPi may not be able to be rescued by another. Lastly, as a proof of principle, HRR proficient ovarian cancer cells were sensitised to PARPis by depletion of BRCA1. In the future, guidelines will need to emerge to assist clinicians in matching specific PARPis to specific patients and tumours.

CXCL10 alters the tumour immune microenvironment and disease progression in a syngeneic murine model of high-grade serous ovarian cancer

2017 ◽  
Vol 145 (3) ◽  
pp. 436-445 ◽  
Author(s):  
Katrina K. Au ◽  
Nichole Peterson ◽  
Peter Truesdell ◽  
Gillian Reid-Schachter ◽  
Kasra Khalaj ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Disease Progression ◽  
Murine Model ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Immune Microenvironment

scholarly journals New cell line models for the development of personalized therapy for high grade serous ovarian cancer

2017 ◽  
Vol 28 ◽  
pp. vii15-vii16
Author(s):  
D. Castillo-Tong ◽  
I. Von Der Decken ◽  
S. Pfaffinger ◽  
A. Wolf ◽  
C. Kreuzinger ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Line ◽  
Personalized Therapy ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
New Cell Line

scholarly journals Cell line and patient-derived xenograft models reveal elevated CDCP1 as a target in high-grade serous ovarian cancer

2016 ◽  
Vol 114 (4) ◽  
pp. 417-426 ◽  
Author(s):  
Brittney S Harrington ◽  
Yaowu He ◽  
Claire M Davies ◽  
Sarah J Wallace ◽  
Mark N Adams ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Line ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Patient Derived Xenograft ◽  
Xenograft Models

scholarly journals Establishment and Characterization of the Novel High-Grade Serous Ovarian Cancer Cell Line OVPA8

2018 ◽  
Vol 19 (7) ◽  
pp. 2080 ◽  
Author(s):  
Patrycja Tudrej ◽  
Magdalena Olbryt ◽  
Ewa Zembala-Nożyńska ◽  
Katarzyna Kujawa ◽  
Alexander Cortez ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Line ◽  
Cancer Cell Lines ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Ovarian Cancer Cell Lines

High-grade serous ovarian carcinoma (HGSOC) is the most frequent histological type of ovarian cancer and the one with worst prognosis. Unfortunately, the majority of established ovarian cancer cell lines which are used in the research have unclear histological origin and probably do not represent HGSOC. Thus, new and reliable models of HGSOC are needed. Ascitic fluid from a patient with recurrent HGSOC was used to establish a stable cancer cell line. Cells were characterized by cytogenetic karyotyping and short tandem repeat (STR) profiling. New generation sequencing was applied to test for hot-spot mutations in 50 cancer-associated genes and fluorescence in situ hybridization (FISH) analysis was used to check for TP53 status. Cells were analyzed for expression of several marker genes/proteins by reverse-transcription polymerase chain reaction (RT-PCR), fluorescence-activated cell sorting (FACS), and immunocytochemistry (ICC). Functional tests were performed to compare OVPA8 cells with five commercially available and frequently used ovarian cancer cell lines: SKOV3, A2780, OVCAR3, ES2, and OAW42. Our newly-established OVPA8 cell line shows morphologic and genetic features consistent with HGSOC, such as epithelial morphology, multiple chromosomal aberrations, TP53 mutation, BRCA1 mutation, and loss of one copy of BRCA2. The OVPA8 line has a stable STR profile. Cells are positive for EpCAM, CK19, and CD44; they have relatively low plating efficiency/ability to form spheroids, a low migration rate, and intermediate invasiveness in matrigel, as compared to other ovarian cancer lines. OVPA8 is sensitive to paclitaxel and resistant to cisplatin. We also tested two FGFR inhibitors; OVPA8 cells were resistant to AZD4547 (AstraZeneca, London, UK), but sensitive to the new inhibitor CPL304-110-01 (Celon Pharma, Łomianki/Kiełpin, Poland). We have established and characterized a novel cell line, OVPA8, which can be a valuable preclinical model for studies on high-grade serous ovarian cancer.

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