Endocrine Abstracts

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...

Background: Adrenocortical carcinoma (ACC) is a rare cancer associated with hereditary syndromes in 10% of cases. However, data on germline variants (GVs) in adult patients with sporadic ACC are limited.Methods: We analyzed germline DNA from 150 adult patients with sporadic ACC sequentially referred to our centers between 1998-2019. We designed a custom panel of 17 genes potentially involved in the pathogenesis of ACC: AIP, APC, ARMC5, ARNT, BRCA1, BRCA2...

Background: Adrenocortical carcinoma (ACC) is a rare cancer for which available systemic treatments, mitotane ± etoposide, doxorubicin and cisplatin (EDP-M), have limited efficacy.Objectives: Here, we strengthen the effect of progesterone (Pg) on metastatic ACC cell lines, studying whether it could influence growth, invasiveness, and metastasis formation. Additionally, we investigate if the Pg analogue megestrol-acetate administered with EDP-M could...

Background: More than 50% of adrenocortical carcinomas (ACC) in adults are associated with cortisol excess that makes tumor management challenging and has a negative impact on patient outcome. Abiraterone acetate (AA) is an irreversible inhibitor of the 17α-hydroxylase/C17, 20-lyase (CYP17 enzyme) that is used in patients with prostate cancer, in whom it leads to suppression of cortisol and androgens. The aim of this study was to assess the activity of AA to control corti...

Background: Adrenocortical cancer (ACC) is a rare malignant neoplasm with a dismal prognosis, particularly in advanced disease. For these patients only limited therapeutic options are available. Adavosertib (AZD1775) is a potent inhibitor of tyrosine kinase WEE1 that regulates cell cycle checkpoints, slowing cell cycle progression and leading to mitotic entry in the presence of DNA damage. Therefore, its use could potentiate existing DNA damage-based therapies. Here, we evalua...

Adrenocortical carcinomas (ACC) are rare endocrine tumors that originate in the cortex of the adrenal gland. They are characterized by the overexpression of insulin-like growth factor 2 (IGF2), whose bond with two tyrosine-kinase receptors, IGF1R and IR, activates a cancer-promoting signalling cascade. Another component of the IGF system is mannose 6-phosphate/insulin-like growth factor 2 receptor (IGF2R), a scavenger receptor able to bind specifically IGF2. Its main role is t...

The majority of adrenocortical carcinomas (ACC) overexpress insulin-like growth factor 2 (IGF2). Although IGF2 drives a proliferative autocrine loop by binding to IGF1R and the isoform A of the insulin receptor (IRA), most studies focused on IGF1R. Recently, a high expression of IRA was observed in ACC vs normal adrenal tissues (NA), suggesting its potential involvement in modulating IGF2 effects in adrenocortical tumorigenesis. Aim of this study was to investigate the specifi...