Adenocarcinoma of Mullerian origin: review of pathogenesis, molecular biology, and emerging treatment paradigms

Cobb, Lauren; Gaillard, Stéphanie; Wang, Yihong; Shih, Ie‐Ming; Secord, Angeles Alvarez

doi:10.1186/s40661-015-0008-z

Cited by 33 publications

(37 citation statements)

References 141 publications

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“…The morphology, in addition to tumor cells staining positive for CK7/PAX8 and negative for ER/WT-1 (not shown), was consistent with the diagnosis of clear cell adenocarcinoma. 13 Whole exome sequencing of the primary tumor sample revealed ERBB2 amplification (Fig. 1c ), which was confirmed by FISH (Fig.…”

Section: Resultsmentioning

confidence: 69%

Case study: patient-derived clear cell adenocarcinoma xenograft model longitudinally predicts treatment response

et al. 2018

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There has been little progress in the use of patient-derived xenografts (PDX) to guide individual therapeutic strategies. In part, this can be attributed to the operational challenges of effecting successful engraftment and testing multiple candidate drugs in a clinically workable timeframe. It also remains unclear whether the ancestral tumor will evolve along similar evolutionary trajectories in its human and rodent hosts in response to similar selective pressures (i.e., drugs). Herein, we combine a metastatic clear cell adenocarcinoma PDX with a timely 3 mouse x 1 drug experimental design, followed by a co-clinical trial to longitudinally guide a patient’s care. Using this approach, we accurately predict response to first- and second-line therapies in so far as tumor response in mice correlated with the patient’s clinical response to first-line therapy (gemcitabine/nivolumab), development of resistance and response to second-line therapy (paclitaxel/neratinib) before these events were observed in the patient. Treatment resistance to first-line therapy in the PDX is coincident with biologically relevant changes in gene and gene set expression, including upregulation of phase I/II drug metabolism (CYP2C18, UGT2A, and ATP2A1) and DNA interstrand cross-link repair (i.e., XPA, FANCE, FANCG, and FANCL) genes. A total of 5.3% of our engrafted PDX collection is established within 2 weeks of implantation, suggesting our experimental designs can be broadened to other cancers. These findings could have significant implications for PDX-based avatars of aggressive human cancers.

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Section: Resultsmentioning

confidence: 69%

Case study: patient-derived clear cell adenocarcinoma xenograft model longitudinally predicts treatment response

et al. 2018

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“…In the case of ovarian cancer, definite knowledge about the histological origin of its cell lines is particularly vital because the disease is very heterogeneous. In fact, recent studies indicate that “ovarian cancer” is a collective term for several pelvic cancers originating from different tissues and having distinct biology, course of disease, and prognosis [ 8 , 9 ]. Preferably, each histological type of ovarian cancer would require its own dedicated model cell lines.…”

Section: Introductionmentioning

confidence: 99%

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

Tudrej

Olbryt

Zembala‐Nożyńska

et al. 2018

IJMS

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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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“…In clear-cell carcinoma, ARID1A gene mutations additionally occur, and in the endometrioid cancer -CTNNB1 gene mutations. Mutations of the KRAS gene are characteristic for the mucinous type [5,6].…”

Section: Heterogeneity Of Ovarian Cancermentioning

confidence: 99%

Characteristics of in vitro model systems for ovarian cancer studies

et al. 2019

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Nowadays, targeted therapy plays a growing role in oncological treatment. In ovarian cancer, particularly promising results are achieved with poly (ADP-ribose) polymerase (PARP) inhibitors. Recent clinical trials have shown that PARP inhibitors can result in significantly longer progression-free survival. These results encourage the search for other targeted therapies and bring hope that ovarian cancer can soon become a manageable chronic disease. The main problem in ovarian cancer research is the heterogeneity of this disease. Recent studies have shown that different histological types of ovarian cancer can originate from distinct tissues. According to the recent knowledge, "ovarian cancer" is an artificial term for distinct invasive malignancies localised within the pelvis. Genetic and immunophenotype analyses have shown that high-grade serous ovarian cancer, the most frequent histological type and the one with the worst prognosis, originates mainly from fallopian tube epithelium, while endometrioid and clear-cell cancers originate from the endometrium. For these reasons, in basic and preclinical studies on ovarian cancer, one has to carefully choose a well-defined model system, corresponding to the histological type of interest. In this article, we discuss ovarian cancer cell lines most frequently used in in vitro studies. Our aim is to indicate the advantages and disadvantages of different models, encompassing primary and established cell cultures, two-and three-dimensional models, etc. In particular, we would like to alert researchers to the fact that the most popular cell lines SKOV3 and A2780 do not represent a suitable model for studies on high-grade serous ovarian cancer.

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Adenocarcinoma of Mullerian origin: review of pathogenesis, molecular biology, and emerging treatment paradigms

Cited by 33 publications

References 141 publications

Case study: patient-derived clear cell adenocarcinoma xenograft model longitudinally predicts treatment response

Case study: patient-derived clear cell adenocarcinoma xenograft model longitudinally predicts treatment response

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

Characteristics of in vitro model systems for ovarian cancer studies

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