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From a therapeutic standpoint, <jats:italic>ATRA<\/jats:italic> is the first example of pharmacological agent exerting its anti-tumor activity via a cell differentiating action. In the clinics, <jats:italic>ATRA<\/jats:italic> is used in the treatment of Acute Promyelocytic Leukemia, a rare form of myeloid leukemia with unprecedented therapeutic results. The extraordinary effectiveness of <jats:italic>ATRA<\/jats:italic> in the treatment of Acute Promyelocytic Leukemia patients has raised interest in evaluating the potential of this natural retinoid in the treatment of other types of neoplasias, with particular reference to solid tumors.<\/jats:p><jats:p>The present article provides an overview of the available pre-clinical and clinical studies focussing on <jats:italic>ATRA<\/jats:italic> as a therapeutic agent in the context of breast cancer from a holistic point of view. In detail, we focus on the direct effects of <jats:italic>ATRA<\/jats:italic> in breast cancer cells as well as the underlying molecular mechanisms of action. In addition, we summarize the available information on the action exerted by <jats:italic>ATRA<\/jats:italic> on the breast cancer micro-environment, an emerging determinant of the progression and invasive behaviour of solid tumors. In particular we discuss the recent evidences of <jats:italic>ATRA<\/jats:italic> activity on the immune system. Finally, we analyse and discuss the results obtained with the few <jats:italic>ATRA<\/jats:italic>-based clinical trials conducted in the context of breast cancer.<\/jats:p>\n                <jats:p><jats:bold>Graphical Abstract<\/jats:bold><\/jats:p>","DOI":"10.1186\/s12964-024-01492-2","type":"journal-article","created":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T13:02:06Z","timestamp":1708002126000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Cellular and micro-environmental responses influencing the antitumor activity of all-trans retinoic acid in breast cancer"],"prefix":"10.1186","volume":"22","author":[{"given":"Maria Azzurra","family":"Caricasulo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Zanetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mineko","family":"Terao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Garattini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Paroni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,15]]},"reference":[{"key":"1492_CR1","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1007\/978-1-4614-0040-0_7","volume-title":"Alcohol and Cancer [internet]","author":"RS Alcohol","year":"2011","unstructured":"Alcohol RS. 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