RAR and RXR modulation in cancer and metabolic disease
Abstract
Retinoic acid receptors (RARs) are ligand-controlled transcription factors that function as heterodimers with retinoid X receptors (RXRs) to regulate cell growth and survival. The success of RAR modulation in the treatment of acute promyelocytic leukaemia (APL) has stimulated considerable interest in the development of RAR and RXR modulators. This has been aided by recent advances in the understanding of the biological role of RARs and RXRs and in the design of selective receptor modulators that might overcome the limitations of current drugs. Here, we discuss the challenges and opportunities for therapeutic strategies based on RXR and RAR modulators, with a focus on cancer and metabolic diseases such as diabetes and obesity.
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Several semi-synthetic and synthetic retinoids have been developed to decrease the toxicity of natural retinoids and to increase their stability and selectivity against a specific RAR subtype.
“To decrease the toxicity of the natural retinoids as well as to increase their stability and selectivity against a specific RAR subtype, several semi-synthetic and synthetic retinoids (including “atypical retinoids”) have been developed29,30.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [29]
At least four molecules have reached phase 4 clinical trials: bexarotene, tazarotene, adapalene, and trifarotene.
“At least four molecules have reached phase 4 clinical trials: bexarotene, tazarotene, adapalene, and trifarotene29–31.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [29]
In most cases, RA-based monotherapies are less efficient in interfering with tumorigenesis and cancer progression than combination therapies.
“In most cases, RA-based monotherapies are less efficient in interfering with tumorigenesis and cancer progression than combination therapies29.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [29]
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le Maire, A., Teyssier, C., Balaguer, P., Bourguet, W., & Germain, P. (2019) · Cells · doi:10.3390/cells8111392 · Cited by 88 · see citing works
Chakrabarti, M., McDonald, A. J., Will Reed, J., Moss, M. A., Das, B. C., & Ray, S. K. (2016) · Journal of Alzheimer's Disease · doi:10.3233/jad-150450 · Cited by 57 · see citing works
Bama, E. S., Grace, V. M. B., Sundaram, V., & Jesubatham, P. D. (2019) · 3 Biotech · doi:10.1007/s13205-019-1692-x · Cited by 8 · see citing works
- Authors
- Altucci, L., Leibowitz, M. D., Ogilvie, K. M., de Lera, A. R., & Gronemeyer, H.
- Affiliations
- University of Campania "Luigi Vanvitelli" (IT)
- Ligand Pharmaceuticals (United States) (US)
- Exelixis (United States) (US)
- Institut de génétique et de biologie moléculaire et cellulaire (FR)
- Corresponding author
- Gronemeyer, Hinrich
- Venue
- Nature Reviews Drug Discovery
- Published
- 2007-10
- Volume
- 6
- Issue
- 10
- Pages
- 793-810
- ISSN
- 1474-1776 (ISSN-L)
- 1474-1784
- OpenAlex
- W2091007186
- Cited by
- 517
- References
- 184
- Citations by year
- 2026: 9 · 2025: 24 · 2024: 13 · 2023: 14 · 2022: 23 · 2021: 16 · 2020: 20 · 2019: 35 · 2018: 25 · 2017: 21 · 2016: 22 · 2015: 24 · 2014: 32 · 2013: 36 · 2012: 43
- FWCI
- 2.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Drug Discovery (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi della Campania "Luigi Vanvitelli" (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- retinoic acid receptor, retinoid X receptor, RAR/RXR heterodimers, acute promyelocytic leukemia, cancer therapy, metabolic disorders, diabetes mellitus, obesity, transcription factors, drug design
- MeSH terms
- Clinical Trials as Topic, Diabetes Mellitus, Humans, Ligands, Neoplasms, Obesity, Retinoids, Receptors, Retinoic Acid, Retinoid X Receptors
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