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Antisecretory and antineoplastic activity of abiraterone in adrenocortical carcinoma: a preclinical and clinical study

Ente finanziatore
AIRC (Associazione Italiana Ricerca sul Cancro)

Aree / Gruppi di ricerca

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Descrizione del progetto

Approximately 50% of adrenocortical carcinoma (ACC) are hormone secreting and cortisol excess (Cushing’s syndrome) is the most common endocrine presentation. Several studies suggested that cortisol excess is a key factor influencing negatively the outcome of patients with metastatic ACC. A rapid control of the endocrine syndrome is therefore advisable. Since ABIRATERONE has been shown to be potent in blocking adrenal steroidogenesis, it may be highly effective for treatment of Cushing’s syndrome associated to ACC. Preliminary in vitro results suggest an anti-proliferative effect of the drug. The aim of the present study is to demonstrate for the first time that ABIRATERONE is effective to obtaining a rapid and effective control of cortisol excess either in preclinical models or in patients with ACC and may also have anti-neoplastic activity. ABIRATERONE will be tested in established ACC cell lines and in primary cultures obtained with surgery. The intracellular pathways modified by ABIRATERONE will be studied in order to detect the key points involved in the mechanism of action using molecular biochemical and pharmacological tools. The clinical phase will be a multicenter phase II study in advanced ACC patients with Cushing’s syndrome to assess the activity of ABIRATERONE in attaining normalization of 24-h urinary free cortisol excretion within 1 month of treatment. The availability of an effective treatment for Cushing’s syndrome in advanced ACC patients may have a significant beneficial impact on either survival and quality of life of patients.
Ultimo aggiornamento: 06/06/2023 10:14
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