Endocrine Abstracts

Context: Adrenocortical carcinoma (ACC) are endocrine malignant neoplasms associated with severe aggressiveness. By applying of ‘multiple omics’ approach, we recently categorized ACC patients based on their steroidogenic activity and expression of immune activation marker, which is along with prognosis; an ‘immune’ phenotype with good and a ‘steroid’ phenotype with bad outcome.Hypothesis: Our central hypothesis focuses on th...

Ad Adrenocortical carcinoma (ACC) is an aggressive tumour and treatment remains unsatisfactory in advanced disease. Activation of epithelial to mesenchymal transition (EMT) is considered causative for metastatic spread in a variety of human cancers. Accordingly, new drugs were developed specifically targeting EMT with a focus on hepatocyte growth factor (HGF)/HGF receptor (c-MET) and fibroblast growth factor (FGF)/FGF receptor (FGFR) signalling.We here a...

Background: Adrenocortical tumours consist of frequent adrenocortical adenomas (ACA) and highly malignant (ACC) with a still incompletely understood pathogenesis. Dysregulation of Notch signalling pathway is implicated in several cancers with oncogenic or tumour suppressor functions. Copy number gains and over-expression of Jagged1, a ligand of Notch receptor, was reported in ACC. The aim of the study was to evaluate the expression of Jagged1 and other Notch-r...

Background: Mitotane is the only approved treatment for advanced adrenocortical carcinoma and was shown to inhibit Sterol-O-Acyl transferase 1 (SOAT1) which leads to the depletion of cholesterol esters and increase of free cholesterol in the ACC cell line H295R. Downstream activation of the endoplasmic reticulum stress (ER-stress) pathway results in decreased adrenocortical cell viability.Aim: To better characterize the effects of SOAT1 inhibition in ACC...

Introduction: Adrenocortical carcinoma (ACC) is an aggressive tumour with unsatisfactory treatment options in advanced disease. Activation of epithelial to mesenchymal transition (EMT) has been described as causative of metastatic spread in human cancers. New drugs were developed targeting EMT with a focus on FGF/FGFR signalling. We here asked whether EMT is relevant in ACC.Methods: We analysed 6 normal adrenal glands (NAG), 40 adrenocortical adenomas (A...

Background: The recent ESE-ENSAT guidelines on adrenocortical carcinoma (ACC) indicated new treatment options for patients with “high risk for recurrence” as one of the major research topics for the field. However, since almost no data were available on the use of cytotoxic drugs in an adjuvant setting, no clear recommendation could be given. Here we report our experience with adjuvant platin-based therapy since 2002 at the University of Würzburg and MD Anders...

Objective: The saline infusion test (SIT) is a standard confirmatory test for primary aldosteronism (PA) and based on impaired aldosterone suppression in PA compared to essential hypertension (EH). In the past, aldosterone was quantified using immunoassays (IA). Due to the more widespread use of liquid chromatography tandem mass spectrometry (LC-MS/MS) in clinical routine, we aimed at a method-specific aldosterone threshold for the diagnosis of PA during SIT and explored the d...

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 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...

Background: Adrenocortical carcinoma (ACC) is a very rare and aggressive, endocrine malignancy with still limited treatment options. Approximately 60% of patients with ACC show endogenous glucocorticoid excess which could be one potential cause, why first clinical trials with immunotherapies, like immune checkpoint inhibitors, showed only modest results. Due to the lack of an ACC-specific antigen structure, other immunotherapeutic approaches, like specialized cancer treatments...