Cellular and micro-environmental responses influencing the antitumor activity of all-trans retinoic acid in breast cancer
Abstract 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 trea...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-02-01
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| Series: | Cell Communication and Signaling |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12964-024-01492-2 |
| _version_ | 1797273831458471936 |
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| author | Maria Azzurra Caricasulo Adriana Zanetti Mineko Terao Enrico Garattini Gabriela Paroni |
| author_facet | Maria Azzurra Caricasulo Adriana Zanetti Mineko Terao Enrico Garattini Gabriela Paroni |
| author_sort | Maria Azzurra Caricasulo |
| collection | DOAJ |
| description | Abstract 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. Graphical Abstract |
| first_indexed | 2024-03-07T14:49:51Z |
| format | Article |
| id | doaj.art-b2f3bf0f31de440d8e1ace0368e9d1b0 |
| institution | Directory Open Access Journal |
| issn | 1478-811X |
| language | English |
| last_indexed | 2024-03-07T14:49:51Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj.art-b2f3bf0f31de440d8e1ace0368e9d1b02024-03-05T19:47:23ZengBMCCell Communication and Signaling1478-811X2024-02-0122112310.1186/s12964-024-01492-2Cellular and micro-environmental responses influencing the antitumor activity of all-trans retinoic acid in breast cancerMaria Azzurra Caricasulo0Adriana Zanetti1Mineko Terao2Enrico Garattini3Gabriela Paroni4Department of Biochemistry and Molecular Pharmacology, Laboratory of Molecular Biology, Istituto di Ricerche Farmacologiche Mario Negri IRCCSDepartment of Biochemistry and Molecular Pharmacology, Laboratory of Molecular Biology, Istituto di Ricerche Farmacologiche Mario Negri IRCCSDepartment of Biochemistry and Molecular Pharmacology, Laboratory of Molecular Biology, Istituto di Ricerche Farmacologiche Mario Negri IRCCSDepartment of Biochemistry and Molecular Pharmacology, Laboratory of Molecular Biology, Istituto di Ricerche Farmacologiche Mario Negri IRCCSDepartment of Biochemistry and Molecular Pharmacology, Laboratory of Molecular Biology, Istituto di Ricerche Farmacologiche Mario Negri IRCCSAbstract 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. Graphical Abstracthttps://doi.org/10.1186/s12964-024-01492-2Retinoic acidBreast cancerTumor micro-environmentDifferentiation therapy |
| spellingShingle | Maria Azzurra Caricasulo Adriana Zanetti Mineko Terao Enrico Garattini Gabriela Paroni Cellular and micro-environmental responses influencing the antitumor activity of all-trans retinoic acid in breast cancer Cell Communication and Signaling Retinoic acid Breast cancer Tumor micro-environment Differentiation therapy |
| title | Cellular and micro-environmental responses influencing the antitumor activity of all-trans retinoic acid in breast cancer |
| title_full | Cellular and micro-environmental responses influencing the antitumor activity of all-trans retinoic acid in breast cancer |
| title_fullStr | Cellular and micro-environmental responses influencing the antitumor activity of all-trans retinoic acid in breast cancer |
| title_full_unstemmed | Cellular and micro-environmental responses influencing the antitumor activity of all-trans retinoic acid in breast cancer |
| title_short | Cellular and micro-environmental responses influencing the antitumor activity of all-trans retinoic acid in breast cancer |
| title_sort | cellular and micro environmental responses influencing the antitumor activity of all trans retinoic acid in breast cancer |
| topic | Retinoic acid Breast cancer Tumor micro-environment Differentiation therapy |
| url | https://doi.org/10.1186/s12964-024-01492-2 |
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