Low-grade serous ovarian cancer: State of the science

Slomovitz, Brian M.; Gourley, Charlie; Carey, Mark; Malpica, Anaís; Shih, Ie Ming; Huntsman, David G.; Fader, Amanda N.; Grisham, Rachel N.; Schlumbrecht, Matthew; Sun, Charlotte C.; Ludemann, Jane; Cooney, Gail Austin; Coleman, Robert L.; Sood, Anil K.; Mahdi, Haider; Wong, Kwong-Kwok; Covens, Allan; O’Malley, David M.; Lécuru, Fabrice; Cobb, Lauren; Caputo, Thomas A.; May, Taymaa; Huang, Marilyn; Siemon, John; Fernández, Marta Llauradó; Ray‐Coquard, Isabelle; Gershenson, David M.

doi:10.1016/j.ygyno.2019.12.033

Cited by 86 publications

(90 citation statements)

References 58 publications

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“…This study was followed up by Fader and colleagues, who also retrospectively explored the use of adjuvant hormonal therapy after surgery without the use of chemotherapy, with promising results [ 83 ]. A phase III trial (NRG GY 019) is now ongoing (initiated in 2019) and is comparing the treatment regimen of Paclitaxel/Carboplatin + Letrozole versus that of Letrozole alone in stage II–IV LGSOC [ 80 ].…”

Section: Targeting Er With Anti-estrogens and Aromatase Inhibitorsmentioning

confidence: 99%

Estrogen Signaling and Its Potential as a Target for Therapy in Ovarian Cancer

Langdon

Herrington

Hollis

et al. 2020

Cancers

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The estrogen receptor (ER) has functionality in selected ovarian cancer subtypes and represents a potential target for therapy. The majority (>80%) of high grade serous, low grade serous and endometrioid carcinomas and many granulosa cell tumors express ER-alpha (ERα), and these tumor types have demonstrated responses to endocrine therapy (tamoxifen and aromatase inhibitors) in multiple clinical studies. Biomarkers of responses to these drugs are actively being sought to help identify responsive cancers. Evidence for both pro-proliferative and pro-migratory roles for ERα has been obtained in model systems. ER-beta (ERβ) is generally considered to have a tumor suppressor role in ovarian cancer cells, being associated with the repression of cell growth and invasion. The differential expression of the specific ERβ isoforms may determine functionality within ovarian cancer cells. The more recently identified G protein-coupled receptor (GPER1; GPR30) has been shown to mediate both tumor-suppressive and tumor-promoting action in ovarian cancer cells, suggesting a more complex role. This review will summarize recent findings in this field.

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Section: Targeting Er With Anti-estrogens and Aromatase Inhibitorsmentioning

confidence: 99%

Estrogen Signaling and Its Potential as a Target for Therapy in Ovarian Cancer

Langdon

Herrington

Hollis

et al. 2020

Cancers

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“…Whereas HGSC frequently arises de novo from tubal or ovarian surface epithelium, most LGSC develop in a stepwise fashion from serous cystadenomas, adenofibromas, and SBT [ 1 , 2 , 4 – 9 ].…”

Section: Morphology and Pathogenesismentioning

confidence: 99%

“…LGSCs are often characterised by KRAS , NRAS , BRAF , USP9X , and EIF1AX mutations [ 1 , 4 , 6 , 9 ]. Also, KRAS mutation may be related to tumour recurrence.…”

Section: Morphology and Pathogenesismentioning

confidence: 99%

Low-grade serous epithelial ovarian cancer: a comprehensive review and update for radiologists

Amante

Santos²,

Cunha³

2021

Insights Imaging

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Low-grade serous carcinoma (LGSC) is an infrequent subtype of ovarian cancer, corresponding to 5% of epithelial neoplasms. This subtype of ovarian carcinoma characteristically has molecular features, pathogenesis, clinical behaviour, sensitivity to chemotherapy, and prognosis distinct to high-grade serous carcinoma (HGSC). Knowing the difference between LGSC and other ovarian serous tumours is vital to guide clinical management, which currently is only possible histologically. However, imaging can provide several clues that allow differentiating LGSC from other tumours and enable precise staging and follow-up of ovarian cancer treatment. Characteristically, LGSC appears as mixed lesions with variable papillary projections and solid components, usually in different proportions from those detected in serous borderline tumour and HGSC. Calcified extracellular bodies, known as psammoma bodies, are also a common feature of LGSC, frequently detectable within lymphadenopathies and metastases associated with this type of tumour. In addition, the characterisation of magnetic resonance imaging enhancement also plays an essential role in calculating the probability of malignancy of these lesions. As such, in this review, we discuss and update the distinct radiological modalities features and the clinicopathologic characteristics of LGSC to allow radiologists to be familiarised with them and to narrow the differential diagnosis when facing this type of tumour.

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“…Notably, in addition to a high proportion of germline BRCA1/2 mutations, HGSC tumors harbor a virtually ubiquitous somatic TP53 mutation (>95%), as well as less commonly mutated genes, including CSMD3 , NF1 , CDK12 , and FAT3 [ 13 , 14 ]. LGSCs, on the other hand, are almost never TP53 -mutated, and instead show high-frequency mutually exclusive mutations in KRAS , BRAF , NRAS , or ERBB2 [ 15 , 16 , 17 ]. CCC tumors often harbor PIK3CA , ARID1A , and KRAS mutations, amongst others, as well as a frequent loss of PTEN expression [ 15 , 16 , 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Modeling the Diversity of Epithelial Ovarian Cancer through Ten Novel Well Characterized Cell Lines Covering Multiple Subtypes of the Disease

Sauriol

Simeone

Portelance

et al. 2020

Cancers

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Cancer cell lines are amongst the most important pre-clinical models. In the context of epithelial ovarian cancer, a highly heterogeneous disease with diverse subtypes, it is paramount to study a wide panel of models in order to draw a representative picture of the disease. As this lethal gynaecological malignancy has seen little improvement in overall survival in the last decade, it is all the more pressing to support future research with robust and diverse study models. Here, we describe ten novel spontaneously immortalized patient-derived ovarian cancer cell lines, detailing their respective mutational profiles and gene/biomarker expression patterns, as well as their in vitro and in vivo growth characteristics. Eight of the cell lines were classified as high-grade serous, while two were determined to be of the rarer mucinous and clear cell subtypes, respectively. Each of the ten cell lines presents a panel of characteristics reflective of diverse clinically relevant phenomena, including chemotherapeutic resistance, metastatic potential, and subtype-associated mutations and gene/protein expression profiles. Importantly, four cell lines formed subcutaneous tumors in mice, a key characteristic for pre-clinical drug testing. Our work thus contributes significantly to the available models for the study of ovarian cancer, supplying additional tools to better understand this complex disease.

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Low-grade serous ovarian cancer: State of the science

Cited by 86 publications

References 58 publications

Estrogen Signaling and Its Potential as a Target for Therapy in Ovarian Cancer

Estrogen Signaling and Its Potential as a Target for Therapy in Ovarian Cancer

Low-grade serous epithelial ovarian cancer: a comprehensive review and update for radiologists

Modeling the Diversity of Epithelial Ovarian Cancer through Ten Novel Well Characterized Cell Lines Covering Multiple Subtypes of the Disease

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