{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T14:20:39Z","timestamp":1761920439750},"reference-count":304,"publisher":"Oxford University Press (OUP)","issue":"2","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:p>Adrenocortical carcinomas (ACCs) are rather rare endocrine tumors that often have a poor prognosis. The reduced survival rate associated with these tumors is due to their aggressive biological behavior, combined with the scarcity of effective treatment options that are currently available. The recent identification of the genomic alterations present in ACC have provided further molecular mechanisms to develop consistent strategies for the diagnosis, prevention of progression and treatment of advanced ACCs. Taken together, molecular and genomic advances could be leading the way to develop personalized medicine in ACCs similarly to similar developments in lung or breast cancers. In this review, we focused our attention to systematically compile and summarize the alterations in the cell cycle regulation that were described so far in ACC as they are known to play a crucial role in cell differentiation and growth. We have divided the analysis according to the major transition phases of the cell cycle, G1 to S and G2 to M. We have analyzed the most extensively studied checkpoints: the p53\/Rb1 pathway, CDC2\/cyclin B and topoisomerases (TOPs). We reached the conclusion that the most important alterations having a potential application in clinical practice are the ones related to p53\/Rb1 and TOP 2. We also present a brief description of on-going clinical trials based on molecular alterations in ACC. The drugs have targeted the insulin-like growth factor receptor 1, TOP 2, polo-like kinase1, cyclin-dependent kinase inhibitors, p53 reactivation and CDC25.<\/jats:p>","DOI":"10.1530\/eje-17-0976","type":"journal-article","created":{"date-parts":[[2018,5,17]],"date-time":"2018-05-17T16:05:14Z","timestamp":1526573114000},"page":"R95-R110","update-policy":"http:\/\/dx.doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":14,"title":["MECHANISMS OF ENDOCRINOLOGY: Cell cycle regulation in adrenocortical carcinoma"],"prefix":"10.1093","volume":"179","author":[{"given":"Sofia S","family":"Pereira","sequence":"first","affiliation":[{"name":"1Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (I3S), Universidade do Porto, Porto, Portugal"},{"name":"2Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal"},{"name":"3Clinical and Experimental Endocrinology, Department of Anatomy, Multidisciplinary Unit for Biomedical Research (UMIB), Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, University of Porto (ICBAS\/UP), Porto, Portugal"}]},{"given":"Mariana P","family":"Monteiro","sequence":"additional","affiliation":[{"name":"3Clinical and Experimental Endocrinology, Department of Anatomy, Multidisciplinary Unit for Biomedical Research (UMIB), Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, University of Porto (ICBAS\/UP), Porto, Portugal"}]},{"given":"Isabelle","family":"Bourdeau","sequence":"additional","affiliation":[{"name":"4Endocrinology Division, Department of Medicine, Centre de Recherche du Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CHUM), Montr\u00e9al, Canada"}]},{"given":"Andr\u00e9","family":"Lacroix","sequence":"additional","affiliation":[{"name":"4Endocrinology Division, Department of Medicine, Centre de Recherche du Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CHUM), Montr\u00e9al, Canada"}]},{"given":"Duarte","family":"Pignatelli","sequence":"additional","affiliation":[{"name":"1Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (I3S), Universidade do Porto, Porto, Portugal"},{"name":"2Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal"},{"name":"5Department of Endocrinology, Hospital S. 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