Endocrine Abstracts

Introduction: Adrenocortical carcinoma (ACC) is one of the most aggressive endocrine malignancies and confers a poor prognosis in advanced stages. Effective treatments are lacking. The results of immune checkpoint inhibition were disappointing with few responders only deriving clinical benefit. For the development of novel immunotherapies such as tumor vaccines and T cell-based treatments, target identification is essential. Tumor-specific mutant neoantigens that may be recogn...

Adrenocortical carcinoma (ACC) is one of the most aggressive endocrine malignancies. By applying a ‘multiple omics’ approach, we recently identified two distinct subgroups of ACC patients, a good prognosis “immune” and bad prognosis “steroid” phenotype.We hypothesized that the steroid phenotype is associated with glucocorticoid-induced suppression that can be ‘rescued’ by reactivating the immune system using immune...

Context: Mitotane (1,1-dichloro-2-[o-chlorophenyl]-2-[p-chlorophenyl]ethane) is the only drug approved for treatment of adrenocortical carcinoma (ACC). Mitotane counteracts both tumor growth and tumoural steroid hormone production but treatment is severely hampered by unfavorable pharmacokinetics and serious side effects. Mitotane is a lipophilic compound and treatment emergent alterations of lipid metabolism are frequently observed. This raises the question whether mitotane d...

Background: Adrenocortical tumors consist of benign adenomas (ACA) and highly malignant carcinomas (ACC). Dysregulation of the Notch signalling pathway is implicated in several cancers with oncogenic or tumor suppressor functions. JAG1 is a Notch1 ligand of the Jagged family and a common target gene for Notch and Wnt/β catenin pathways. It has been reported that upregulated expression of JAG1 enhances cell proliferation in ACC.Material and methods: ...

Introduction: Adrenocortical tumors consist in frequent benign adenomas (ACA) and rare highly malignant carcinomas (ACC). BIRC7/livin gene, a member of the inhibitors of apoptosis family, plays an important role in tumorigenesis in a variety of malignancies. Different studies demonstrated that BIRC7 overexpression represent a risk factor for cancer development and progression. The aim of our study was to evaluate the expression of BIRC7 in normal adrenals and adrenocortical tu...

Context: Adrenocortical carcinoma (ACC) are endocrine malignant neoplasms associated with severe aggressiveness. Tumour-related glucocorticoid excess occurs in 60% of patients and is associated with poor prognosis. First clinical trials using immune checkpoint inhibitors are quite unsatisfactory and treatment advancements are urgently needed.Recently, we characterized tumour-infiltrating lymphocytes (TILs) in ACC and identified the detrimental dependency...

Background: Adrenocortical tumors consist of benign adenomas (ACA) and highly malignant carcinomas (ACC) with a still incompletely understood pathogenesis. Our aim was to test, whether there is evidence for an adenoma-carcinoma sequence.Patients and methods: High-resolution single nucleotide polymorphism (SNP) microarrays (Affymetrix SNP 6.0) were used to detect copy number alterations (CNAs) and copy neutral losses of heterozygosity (cnLOH) in 46 adreno...

Introduction: Streptozotocin (SZ) is an active drug for the treatment of advanced adrenocortical carcinoma (ACC) in a minority of patients with an objective response rate of <10%. It has been reported that expression of glucose transporter-2 (GLUT-2) is essential for SZ to enter tumor cells and that high activity of O-6-methylguanine-DNA methyltransferase (MGMT) counteracts the alkylating effect of SZ. Therefore, we aimed to clarify the role of GLUT-2 and MGMT in the respo...

Background: Immune checkpoint therapy response rate in adrenocortical carcinoma (ACC) is only ~15%. Glucocorticoid (GC) secretion is present in ~60% of tumours, associated with adverse outcome and has been associated with an immunologically cold tumoural microenvironment. On the other hand, activation of the Wnt/ß-Catenin pathway has been suggested to contribute to reduced immune infiltration.Aims: First, we aim to improve the understanding of cellu...

Adrenocortical carcinoma (ACC) is a very severe endocrine malignancy with poor prognosis. While cancer immunotherapies have revolutionized the treatment of several cancer entities, the results of initial studies of different immune checkpoint inhibitors in ACC were heterogeneous and clinically substantial responses were observed only in a subset of patients. Expression of immune checkpoint molecules - programmed cell death 1 (PD-1) and its ligand PD-L1 - has been shown to pred...