Department of Biochemistry and Molecular Pharmacology, Laboratory of Molecular Biology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri, 2, Milan, 20156, Italy.
Cell Commun Signal. 2024 Feb 15;22(1):127. doi: 10.1186/s12964-024-01492-2.
All-trans retinoic acid (ATRA) is the most relevant and functionally active metabolite of Vitamin-A. From a therapeutic standpoint, ATRA is the first example of pharmacological agent exerting its anti-tumor activity via a cell differentiating action. In the clinics, ATRA is used in the treatment of Acute Promyelocytic Leukemia, a rare form of myeloid leukemia with unprecedented therapeutic results. The extraordinary effectiveness of ATRA 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.The present article provides an overview of the available pre-clinical and clinical studies focussing on ATRA 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 ATRA 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 ATRA 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 ATRA activity on the immune system. Finally, we analyse and discuss the results obtained with the few ATRA-based clinical trials conducted in the context of breast cancer.
全反式维甲酸（ATRA）是维生素 A 最相关和最具功能活性的代谢物。从治疗的角度来看，ATRA 是第一个通过细胞分化作用发挥其抗肿瘤活性的药理制剂的例子。在临床上，ATRA 用于治疗急性早幼粒细胞白血病，这是一种罕见的髓样白血病，具有前所未有的治疗效果。ATRA 在治疗急性早幼粒细胞白血病患者中的非凡疗效引起了人们对评估这种天然视黄醇在治疗其他类型肿瘤（特别是实体肿瘤）方面的潜在价值的兴趣。本文从整体角度概述了现有针对 ATRA 作为治疗剂在乳腺癌中的临床前和临床研究，详细介绍了 ATRA 对乳腺癌细胞的直接作用以及其作用的潜在分子机制。此外，我们总结了关于 ATRA 对乳腺癌微环境作用的现有信息，这是实体肿瘤进展和侵袭行为的一个新兴决定因素。特别是，我们讨论了 ATRA 对免疫系统的最新活性证据。最后，我们分析和讨论了在乳腺癌背景下进行的少数基于 ATRA 的临床试验的结果。
