title: Molecular pathways of human adrenocortical carcinoma - translating cell signalling knowledge into diagnostic and treatment options.
abstract: Adrenocortical carcinoma is associated with a low cure rate and a high recurrence rate. The prognosis is poor, and at diagnosis 30-40% of cases are already metastatic. The current therapeutic options (surgical resection, followed by adjuvant mitotane treatment +/- chemotherapy) are limited, and the results remain unsatisfactory. Key molecular events that contribute to formation of adrenocortical cancer are IGF2 overexpression, TP53-inactivating mutations, and constitutive activation of the Wnt/b-catenin signalling pathway via activating mutations of the b-catenin gene. The underlying genetic causes of inherited tumour syndromes have provided insights into molecular pathogenesis. The increased occurrence of adrenocortical tumours in Li-Fraumeni and Beckwith-Wiedemann syndromes, and Carney complex, has highlighted the roles of specific susceptibility genes: TP53, IGF2, and PRKAR1A, respectively. Further studies have confirmed that these genes are also involved in sporadic tumour cases. Crucially, transcriptome-wide studies have determined the differences between malignant and benign adrenocortical tumours, providing potential diagnostic tools. In conclusion, enhancing our understanding of the molecular events of adrenocortical tumourigenesis, especially with regard to the signalling pathways that may be disrupted, will greatly contribute to improving a range of available diagnostic, prognostic, and treatment approaches. (Endokrynol Pol 2016; 67 (4): 427-440).
authors.forename: Paulina
authors.initials: P
authors.lastname: Szyszka
authors.forename: Ashley B
authors.initials: AB
authors.lastname: Grossman
authors.forename: Salvador
authors.initials: S
authors.lastname: Diaz-Cano
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Sworczak
authors.affiliation: Department of Nuclear Medicine, Medical University of Gdansk, Gdansk, Poland; Department of Endocrinology and Medicine, King's College Hospital, London, United Kingdom; Guys Richard Dimbleby Department of Cancer Research, King's College London, London, United Kingdom. ddw@gumed.edu.pl.
authors.forename: Dorota
authors.initials: D
authors.lastname: Dworakowska
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D018268:Adrenocortical Carcinoma / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009154:Mutation; D015398:Signal Transduction
keywords: adrenal cortex neoplasms; adrenocortical carcinoma; hereditary neoplastic syndromes; molecular pathology; molecular targeted therapy; signal transduction pathways