{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T11:48:39Z","timestamp":1769600919085,"version":"3.49.0"},"reference-count":83,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/MEC-ONC\/31384\/2017"],"award-info":[{"award-number":["PTDC\/MEC-ONC\/31384\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/00215\/2020"],"award-info":[{"award-number":["UIDB\/00215\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDP\/00215\/2020"],"award-info":[{"award-number":["UIDP\/00215\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Angiogenesis plays an important role in several physiological and pathological processes. Pharmacological angiogenesis modulation has been robustly demonstrated to achieve clinical benefits in several cancers. Adrenocortical carcinomas (ACC) are rare tumors that often have a poor prognosis. In addition, therapeutic options for ACC are limited. Understanding the mechanisms that regulate adrenocortical angiogenesis along the embryonic development and in ACC could provide important clues on how these processes could be pharmacologically modulated for ACC treatment. In this report, we performed an integrative review on adrenal cortex angiogenesis regulation in physiological conditions and ACC. During embryonic development, adrenal angiogenesis is regulated by both VEGF and Ang-Tie signaling pathways. In ACC, early research efforts were focused on VEGF signaling and this pathway was identified as a good prognostic factor and thus a promising therapeutic target. However, every clinical trial so far conducted in ACC using VEGF pathway- targeting drugs, alone or in combination, yielded disappointing results. In contrast, although the Ang-Tie pathway has been pointed out as an important regulator of fetal adrenocortical angiogenesis, its role is yet to be explored in ACC. In the future, further research on the role and efficacy of modulating both Ang-Tie and VEGF pathways in ACC is needed.<\/jats:p>","DOI":"10.3390\/cancers13051030","type":"journal-article","created":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T10:25:18Z","timestamp":1614594318000},"page":"1030","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Angiogenesis in the Normal Adrenal Fetal Cortex and Adrenocortical Tumors"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6947-4560","authenticated-orcid":false,"given":"Sofia S.","family":"Pereira","sequence":"first","affiliation":[{"name":"Department of Anatomy, Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, University of Porto, 4050-313 Porto, Portugal"},{"name":"Clinical and Experimental Endocrinology, Multidisciplinary Unit for Biomedical Research (UMIB), 4050-313 Porto, Portugal"},{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (I3S), Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology, University of Porto (IPATIMUP), 4200-135 Porto, Portugal"}]},{"given":"Sofia","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, University of Porto, 4050-313 Porto, Portugal"},{"name":"Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0662-1831","authenticated-orcid":false,"given":"Mariana P.","family":"Monteiro","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, University of Porto, 4050-313 Porto, Portugal"},{"name":"Clinical and Experimental Endocrinology, Multidisciplinary Unit for Biomedical Research (UMIB), 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6947-4560","authenticated-orcid":false,"given":"Duarte","family":"Pignatelli","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (I3S), Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology, University of Porto (IPATIMUP), 4200-135 Porto, Portugal"},{"name":"Department of Endocrinology, Hospital S. Jo\u00e3o, 4200-319 Porto, Portugal"},{"name":"Department of Biomedicine, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1046\/j.1087-0024.2000.00014.x","article-title":"Angiogenesis in wound healing","volume":"5","author":"Tonnesen","year":"2000","journal-title":"J. Investig. Dermatol. Symp. Proc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1146\/annurev-cellbio-092910-154002","article-title":"Developmental and Pathological Angiogenesis","volume":"27","author":"Chung","year":"2011","journal-title":"Annu. Rev. Cell Dev. 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