Retinoids as Chemo-Preventive and Molecular-Targeted Anti-Cancer Therapies
Retinoic acid (RA) agents possess anti-tumor activity through their ability to induce cellular differentiation. However, retinoids have not yet been translated into effective systemic treatments for most solid tumors. RA signaling is mediated by the following two nuclear retinoic receptor subtypes:...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/14/7731 |
| _version_ | 1797526923509760000 |
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| author | Victoria O. Hunsu Caroline O. B. Facey Jeremy Z. Fields Bruce M. Boman |
| author_facet | Victoria O. Hunsu Caroline O. B. Facey Jeremy Z. Fields Bruce M. Boman |
| author_sort | Victoria O. Hunsu |
| collection | DOAJ |
| description | Retinoic acid (RA) agents possess anti-tumor activity through their ability to induce cellular differentiation. However, retinoids have not yet been translated into effective systemic treatments for most solid tumors. RA signaling is mediated by the following two nuclear retinoic receptor subtypes: the retinoic acid receptor (RAR) and the retinoic X receptor (RXR), and their isoforms. The identification of mutations in retinoid receptors and other RA signaling pathway genes in human cancers offers opportunities for target discovery, drug design, and personalized medicine for distinct molecular retinoid subtypes. For example, chromosomal translocation involving <i>RARA</i> occurs in acute promyelocytic leukemia (APL), and all-trans retinoic acid (ATRA) is a highly effective and even curative therapeutic for APL patients. Thus, retinoid-based target discovery presents an important line of attack toward designing new, more effective strategies for treating other cancer types. Here, we review retinoid signaling, provide an update on retinoid agents and the current clinical research on retinoids in cancer, and discuss how the retinoid pathway genotype affects the ability of retinoid agents to inhibit the growth of colorectal cancer (CRC) cells. We also deliberate on why retinoid agents have not shown clinical efficacy against solid tumors and discuss alternative strategies that could overcome the lack of efficacy. |
| first_indexed | 2024-03-10T09:36:14Z |
| format | Article |
| id | doaj.art-5b91b612d03c4710a85327c90cb7f7e8 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T09:36:14Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-5b91b612d03c4710a85327c90cb7f7e82023-11-22T04:03:16ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-07-012214773110.3390/ijms22147731Retinoids as Chemo-Preventive and Molecular-Targeted Anti-Cancer TherapiesVictoria O. Hunsu0Caroline O. B. Facey1Jeremy Z. Fields2Bruce M. Boman3Center for Translational Cancer Research, Helen F. Graham Cancer Center & Research Institute, Newark, DE 19713, USACenter for Translational Cancer Research, Helen F. Graham Cancer Center & Research Institute, Newark, DE 19713, USACA*TX Inc., Princeton, NJ 08540, USACenter for Translational Cancer Research, Helen F. Graham Cancer Center & Research Institute, Newark, DE 19713, USARetinoic acid (RA) agents possess anti-tumor activity through their ability to induce cellular differentiation. However, retinoids have not yet been translated into effective systemic treatments for most solid tumors. RA signaling is mediated by the following two nuclear retinoic receptor subtypes: the retinoic acid receptor (RAR) and the retinoic X receptor (RXR), and their isoforms. The identification of mutations in retinoid receptors and other RA signaling pathway genes in human cancers offers opportunities for target discovery, drug design, and personalized medicine for distinct molecular retinoid subtypes. For example, chromosomal translocation involving <i>RARA</i> occurs in acute promyelocytic leukemia (APL), and all-trans retinoic acid (ATRA) is a highly effective and even curative therapeutic for APL patients. Thus, retinoid-based target discovery presents an important line of attack toward designing new, more effective strategies for treating other cancer types. Here, we review retinoid signaling, provide an update on retinoid agents and the current clinical research on retinoids in cancer, and discuss how the retinoid pathway genotype affects the ability of retinoid agents to inhibit the growth of colorectal cancer (CRC) cells. We also deliberate on why retinoid agents have not shown clinical efficacy against solid tumors and discuss alternative strategies that could overcome the lack of efficacy.https://www.mdpi.com/1422-0067/22/14/7731retinoic acidcancer stem cellsadenomatous polyposis colialdehyde dehydrogenasemolecular targeted therapies |
| spellingShingle | Victoria O. Hunsu Caroline O. B. Facey Jeremy Z. Fields Bruce M. Boman Retinoids as Chemo-Preventive and Molecular-Targeted Anti-Cancer Therapies International Journal of Molecular Sciences retinoic acid cancer stem cells adenomatous polyposis coli aldehyde dehydrogenase molecular targeted therapies |
| title | Retinoids as Chemo-Preventive and Molecular-Targeted Anti-Cancer Therapies |
| title_full | Retinoids as Chemo-Preventive and Molecular-Targeted Anti-Cancer Therapies |
| title_fullStr | Retinoids as Chemo-Preventive and Molecular-Targeted Anti-Cancer Therapies |
| title_full_unstemmed | Retinoids as Chemo-Preventive and Molecular-Targeted Anti-Cancer Therapies |
| title_short | Retinoids as Chemo-Preventive and Molecular-Targeted Anti-Cancer Therapies |
| title_sort | retinoids as chemo preventive and molecular targeted anti cancer therapies |
| topic | retinoic acid cancer stem cells adenomatous polyposis coli aldehyde dehydrogenase molecular targeted therapies |
| url | https://www.mdpi.com/1422-0067/22/14/7731 |
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