Endocrine Abstracts

Adrenocortical carcinomas (ACC) are associated with heterogeneous prognosis and limited treatment options for advanced stages. Until now no efficient targeted therapies have been identified. This study aims to identify possible new molecular drug targets for a future personalized therapeutic approach. We isolated good quality RNA from 40 formalin-fixed paraffin-embedded tumor samples (33 from primary surgery, 5 from local recurrences and 2 from distant metastasis) of ACC patie...

Background: Adrenocortical carcinoma (ACC) is one of the most aggressive endocrine malignancies. The Fibroblast Growth Factor/Fibroblast Growth Factor Receptor (FGF/FGFR) pathway plays a role in both embryogenesis and tumorigenesis of adrenal gland. Our group demonstrated that FGFR1-4 were upregulated in ACCs and that their high expression was significantly associated with worse prognosis, suggesting that they are potentially interesting therapeutic targets.<p class="abste...

BackgroundAdrenocortical carcinoma (ACC) is a rare but devastating tumour of the adrenal gland and the molecular mechanisms of pathogenesis remain incompletely understood. To gain novel insights into the cellular landscape of ACC, we compared single nuclei RNA sequencing (snRNA-seq) datasets from ACC and normal adrenal glands (NAGs).Methods: We isolated single nuclei from 12 ACC snap-frozen samples, including 6 primary tumours, 3 local r...

Introduction: Methylation of FKBP5, a glucocorticoid(GC)-receptor co-chaperone, negatively correlates with cortisol levels in both healthy and hypercortisolaemic individuals, and may serve as an indicator of GC exposure. We explored whether GC replacement correlates with FKBP5 methylation levels in patients with adrenal insufficiency (AI), aiming to assess the adequacy of substitution therapy.Methods: In 122 patients with chronic primary (n=73) ...

Background: Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine disease in which 60% of patients show endogenous glucocorticoid (GC) secretion that potentially contributes to a lack of immune cell infiltration and limited efficacy of immunotherapeutic approaches. In another study, we already demonstrated potent antitumor efficacy or ROR1 CAR-T cells in preclinical models of ACC. Nevertheless, solid tumors often show cell intrinsic resistance mechanisms to CAR-T c...

Adrenocortical carcinoma (ACC) is a rare aggressive cancer with heterogeneous behaviour. Disease surveillance relies on frequent imaging, which comes with significant radiation exposure. Here we investigated the role of circulating cell-free DNA (ccfDNA) in ACC monitoring. We extracted ccfDNA from 1-4 ml EDTA-plasma using the Nonacus Cell3TMXtract or the Qiagen QIAamp MinElute kit and quantified by fluorimeter. We investigated 63 patients with ACC (25M/38F, 52±...

Adrenocortical carcinoma (ACC) is an aggressive malignancy with limited treatment options. We identified polo-like kinase 1 (PLK1) as one of the most overexpressed genes and potential drug target in ACC. PLK1 inhibitors (PLK1i) are under evaluation in clinical trials for other malignancies, being more effective in TP53-mutated tumours. Here we test PLK1i efficacy in four ACC cell lines with different genetic background. Efficacy of three PLK1i (i.e. Volaserti...

Background: Molecular mechanisms underlying the pathogenesis of adrenocortical adenomas (ACAs) and autonomous cortisol secretion remains frequently unexplained despite previous comprehensive genomics studies.Aim: To gain novel insights into molecular pathogenesis of adrenocortical tumours by investigating transcriptome profiles of ACAs at single-nuclei resolution (snRNA-Seq), using adult human normal adrenal glands (NAGs) as reference.<p class="abste...

Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine neoplasia with heterogeneous molecular background and clinical outcome. Previous studies identified hypermethylation in specific genes to be associated with poor prognosis. Here, we aimed to investigate the role of methylation pattern for prognostic stratification of patients with ACC as compared to clinical parameters, using methods easily applicable in clinical routine. We investigated a total of 237 ACCs (96 ...

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy. ACC may rarely occur as part of familial cancer syndromes, but the majority of the cases occur sporadically. A significant proportion of sporadic ACC cases may be preceded by other malignancies and adrenal metastasis from these primary tumours may frequently occur. Herein we present three cases where sporadic ACC was identified in patients with coexistent or previous history of melanoma.Case ...