Targeting TGF β pathway in Adult Granulosa Cell Tumor: Opening Pandora's Box?

Targeting TGFβ pathway in Adult Granulosa Cell Tumor: Opening Pandora's Box? Clin Cancer Res. 2019 Jul 11;: Authors: Bonilla L, Oza AM Abstract Adult granulosa cell tumor (AGCT) is a rare malignancy characterized by FOXL2 (C134W) mutation, an inherent component of the TGFβ pathway. Activin A, a TGFβ superfamily member, is a driver of this activity and is a potential target in AGCT. PMID: 31296528 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research

Related Links:

ConclusionJuvenile tGrCT represent a benign entity whereas adult tGCTs have metastatic potential. Tumor size, presence of angiolymphatic invasion or gynecomastia represent risk factors for metastatic disease. The published literature supports the use of testis sparing surgery but there is only limited experience with adjuvant therapies. In the metastatic setting, the reviewed literature suggests that aggressive surgical and systemic treatment might cure patients.
Source: Journal of Cancer Research and Clinical Oncology - Category: Cancer & Oncology Source Type: research
Establishing reliable prognostic factors as well as specific targets for new therapeutic approaches is an urgent requirement in advanced ovarian cancer. For several tumor entities, the ubiquitously spread scaffold protein β-arrestin 2, a multifunctional scaffold protein regulating signal transduction and internalization of activated G protein-coupled receptors (GPCRs), has been considered with rising interest for carcinogenesis. Therefore, we aimed to elucidate the prognostic impact of β-arrestin 2 and its functional role in ovarian cancer. β-arrestin 2 expression was analyzed in a subset of 156 samples of o...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
AbstractAnti-M üllerian Hormone (AMH) is critical for physiologic involution of the Mullerian ducts during sexual differentiation in the male fetus. In women, AMH is a product of the small antral follicles in the ovaries and serves to function as an autocrine and paracrine regulator of follicular maturation. As t he size of the residual follicular pool depends on the quantity of small antral follicles and declines over time, the serum AMH level in women follows a characteristic trajectory: a gradual decline throughout the reproductive years and a precipitous drop at menopause, becoming undetectable soon afte r. Thus, ...
Source: The Journal of Obstetrics and Gynecology of India - Category: OBGYN Source Type: research
Only one of seven eligible patients underwent intraperitoneal chemotherapy in our large heterogenous health system. Intraperitoneal chemotherapy use has been associated with improved 10 ‐year survival, but not necessarily recurrence benefit compared to intravenous chemotherapy. AbstractBackgroundIntraperitoneal/intravenous chemotherapy (IP/IV) was associated with improved survival for ovarian cancer (OC) patients in several randomized clinical trials. However, the uptake of IP/IV in clinical practice is varied due to conflicting evidence about its impact on survival and recurrence. The aim of this study was to explore th...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
Contributor : Paul A CloosSeries Type : Expression profiling by high throughput sequencing ; Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensThe FOXL2 mutant C134W occurs in virtually all adult ovarian granulosa cell tumors (AGCT), and is considered a driver of oncogenesis in this disease. However, the mechanism by which FOXL2C134W contributes to tumorigenesis is not known. Here, we show that mutant FOXL2C134W acquires the ability to bind SMAD4, forming a FOXL2C134W/SMAD4/SMAD2/3 complex that binds a novel hybrid DNA motif AGHCAHAA, unique to the FOXL2C134W mutant. This binding induce...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing Homo sapiens Source Type: research
Gourley 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 obta...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
In this study, potentially targetable genomic alterations in AGCTs were investigated by whole genome sequencing on 46 tumor samples and matched normal DNA. Copy number variant (CNV) analysis confirmed gain of chromosome 12 and 14, and loss of 22. Pathogenic TP53 mutations were identified in three patients with highest tumor mutational burden and mitotic activity, defining a high-grade AGCT subgroup. Within-patient tumor comparisons showed 29–80% unique somatic mutations per sample, suggesting tumor heterogeneity. A higher mutational burden was found in recurrent tumors, as compared to primary AGCTs. FOXL2-wildtyp...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
et A, Berton D, Kalbacher E, Chakiba C, Meeus P, Selle F, Treilleux I, Lecuru F, Pautier P, Ray-Coquard I Abstract OBJECTIVE: The French national rare gynecological tumor network has been established to improve the quality of care through offering expertise in double reading histological diagnosis, reviewing cases and guiding management of these tumors through specialized multidisciplinary tumor boards and online clinical guidelines (www.ovaire-rare.com). The aim of this study is to evaluate the impact of the development and implementation of this network by assessing the conformity of medical practice with the gu...
Source: Gynecologic Oncology - Category: Cancer & Oncology Authors: Tags: Gynecol Oncol Source Type: research
This study aimed to investigate the effects of a mixture of endocrine-disrupting chemicals (EDCs) on secretion of IGF1 by COV434 and KGN cells, which have been used as in vitro models of juvenile and adult GCTs, respectively. The EDC mixture contained perfluorooctanoate, perfluorooctane sulfonate, 2,2-dichlorodiphenyldichloroethylene, hexachlorobenzene, and polychlorinated biphenyl 153, which are persistent hormonally active environmental toxicants present in ovarian follicular fluid (FF). Expression and secretion of IGF1 were significantly higher in GTCs than in HGrC1 human non-cancer granulosa cells (with the profile HGrC1 
Source: Toxicology in Vitro - Category: Toxicology Authors: Tags: Toxicol In Vitro Source Type: research
Sumaira Qayoom, Malti Kumari, Sameer Gupta, Madhumati GoelJournal of Cancer Research and Therapeutics 2019 15(5):1186-1188 Breast cancer is one of the main sources of ovarian metastasis. Diffuse sheet of lobular carcinoma cells can strongly mimic granulosa cell tumor (GCT) which itself is a rare ovarian neoplasm constituting <5% of all the ovarian neoplasms. A 55-year-old female presented with a painful lump in the right breast associated with nipple discharge for 4 months, which on radiological and cytological findings was suspicious of an epithelial malignancy. During routine work-up, a solid-cystic lesion in th...
Source: Journal of Cancer Research and Therapeutics - Category: Cancer & Oncology Authors: Source Type: research
More News: Cancer | Cancer & Oncology | Granulosa Cell Tumor