The Use of Retinoids for the Prevention and Treatment of Skin Cancers: An Updated Review

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Oct 27

PMID 36293471

Authors

Brandon Ramchatesingh

Amelia Martinez Villarreal

Domenico Arcuri

Francois Lagace

Samy Abu Setah

Fadi Touma

Faris Al-Badarin

Ivan V Litvinov

Affiliations

Soon will be listed here.

Abstract

Retinoids are natural and synthetic vitamin A derivatives that are effective for the prevention and the treatment of non-melanoma skin cancers (NMSC). NMSCs constitute a heterogenous group of non-melanocyte-derived skin cancers that impose substantial burdens on patients and healthcare systems. They include entities such as basal cell carcinoma and cutaneous squamous cell carcinoma (collectively called keratinocyte carcinomas), cutaneous lymphomas and Kaposi's sarcoma among others. The retinoid signaling pathway plays influential roles in skin physiology and pathology. These compounds regulate diverse biological processes within the skin, including proliferation, differentiation, angiogenesis and immune regulation. Collectively, retinoids can suppress skin carcinogenesis. Both topical and systemic retinoids have been investigated in clinical trials as NMSC prophylactics and treatments. Desirable efficacy and tolerability in clinical trials have prompted health regulatory bodies to approve the use of retinoids for NMSC management. Acceptable off-label uses of these compounds as drugs for skin cancers are also described. This review is a comprehensive outline on the biochemistry of retinoids, their activities in the skin, their effects on cancer cells and their adoption in clinical practice.

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References

Ghazawi F, Netchiporouk E, Rahme E, Tsang M, Moreau L, Glassman S . Comprehensive analysis of cutaneous T-cell lymphoma (CTCL) incidence and mortality in Canada reveals changing trends and geographic clustering for this malignancy. Cancer. 2017; 123(18):3550-3567. DOI: 10.1002/cncr.30758. View

Bastien J, Rochette-Egly C . Nuclear retinoid receptors and the transcription of retinoid-target genes. Gene. 2004; 328:1-16. DOI: 10.1016/j.gene.2003.12.005. View

Hatoum A, El-Sabban M, Khoury J, Yuspa S, Darwiche N . Overexpression of retinoic acid receptors alpha and gamma into neoplastic epidermal cells causes retinoic acid-induced growth arrest and apoptosis. Carcinogenesis. 2001; 22(12):1955-63. DOI: 10.1093/carcin/22.12.1955. View

Gill R, Gantchev J, Martinez Villarreal A, Ramchatesingh B, Netchiporouk E, Akilov O . Understanding Cell Lines, Patient-Derived Xenograft and Genetically Engineered Mouse Models Used to Study Cutaneous T-Cell Lymphoma. Cells. 2022; 11(4). PMC: 8870189. DOI: 10.3390/cells11040593. View

van de Glind G, Out-Luiting J, Rebel H, Tensen C, de Gruijl F . Lgr5+ stem cells and their progeny in mouse epidermis under regimens of exogenous skin carcinogenesis, and their absence in ensuing skin tumors. Oncotarget. 2016; 7(32):52085-52094. PMC: 5239536. DOI: 10.18632/oncotarget.10475. View

Cattelan L, Ghazawi F, Le M, Lagace F, Savin E, Zubarev A . Epidemiologic trends and geographic distribution of esophageal cancer in Canada: A national population-based study. Cancer Med. 2019; 9(1):401-417. PMC: 6943153. DOI: 10.1002/cam4.2700. View

Geskin L, Malone D . An exploratory cost-effectiveness analysis of systemic treatments for cutaneous T-cell lymphoma. J Dermatolog Treat. 2017; 29(5):522-530. DOI: 10.1080/09546634.2017.1412064. View

Sorg O, Tran C, Carraux P, Grand D, Hugin A, Didierjean L . Spectral properties of topical retinoids prevent DNA damage and apoptosis after acute UV-B exposure in hairless mice. Photochem Photobiol. 2005; 81(4):830-6. DOI: 10.1111/j.1751-1097.2005.tb01450.x. View

Passeri D, Doldo E, Tarquini C, Costanza G, Mazzaglia D, Agostinelli S . Loss of CRABP-II Characterizes Human Skin Poorly Differentiated Squamous Cell Carcinomas and Favors DMBA/TPA-Induced Carcinogenesis. J Invest Dermatol. 2016; 136(6):1255-1266. DOI: 10.1016/j.jid.2016.01.039. View

10.

Zhang C, Duvic M . Treatment of cutaneous T-cell lymphoma with retinoids. Dermatol Ther. 2006; 19(5):264-71. DOI: 10.1111/j.1529-8019.2006.00083.x. View

11.

Gibbs S, Backendorf C, Ponec M . Regulation of keratinocyte proliferation and differentiation by all-trans-retinoic acid, 9-cis-retinoic acid and 1,25-dihydroxy vitamin D3. Arch Dermatol Res. 1996; 288(12):729-38. DOI: 10.1007/BF02505289. View

12.

Heald P, Mehlmauer M, Martin A, Crowley C, Yocum R, Reich S . Topical bexarotene therapy for patients with refractory or persistent early-stage cutaneous T-cell lymphoma: results of the phase III clinical trial. J Am Acad Dermatol. 2003; 49(5):801-15. DOI: 10.1016/s0190-9622(03)01475-0. View

13.

Bailly C, Dreze S, Asselineau D, Nusgens B, Lapiere C, Darmon M . Retinoic acid inhibits the production of collagenase by human epidermal keratinocytes. J Invest Dermatol. 1990; 94(1):47-51. DOI: 10.1111/1523-1747.ep12873342. View

14.

Breneman D, Duvic M, Kuzel T, Yocum R, Truglia J, Stevens V . Phase 1 and 2 trial of bexarotene gel for skin-directed treatment of patients with cutaneous T-cell lymphoma. Arch Dermatol. 2002; 138(3):325-32. DOI: 10.1001/archderm.138.3.325. View

15.

Peck G, DiGiovanna J, Sarnoff D, GROSS E, Butkus D, OLSEN T . Treatment and prevention of basal cell carcinoma with oral isotretinoin. J Am Acad Dermatol. 1988; 19(1 Pt 2):176-85. DOI: 10.1016/s0190-9622(88)70162-0. View

16.

Sabichi A, Xu H, Fischer S, Zou C, Yang X, Steele V . Retinoid receptor-dependent and independent biological activities of novel fenretinide analogues and metabolites. Clin Cancer Res. 2003; 9(12):4606-13. View

17.

Huang C, Ma W, Dawson M, Rincon M, Flavell R, Dong Z . Blocking activator protein-1 activity, but not activating retinoic acid response element, is required for the antitumor promotion effect of retinoic acid. Proc Natl Acad Sci U S A. 1997; 94(11):5826-30. PMC: 20865. DOI: 10.1073/pnas.94.11.5826. View

18.

Sanquer S, Gilchrest B . Characterization of human cellular retinoic acid-binding proteins-I and -II: ligand binding affinities and distribution in skin. Arch Biochem Biophys. 1994; 311(1):86-94. DOI: 10.1006/abbi.1994.1212. View

19.

Popadic S, Ramic Z, Medenica L, Mostarica Stojkovic M, Trajkovic V, Popadic D . Antiproliferative effect of vitamin A and D analogues on adult human keratinocytes in vitro. Skin Pharmacol Physiol. 2008; 21(4):227-34. DOI: 10.1159/000135639. View

20.

Nieto-Rementeria N, Perez-Yarza G, Boyano M, Apraiz A, Izu R, Diaz-Perez J . Bexarotene activates the p53/p73 pathway in human cutaneous T-cell lymphoma. Br J Dermatol. 2008; 160(3):519-26. DOI: 10.1111/j.1365-2133.2008.08931.x. View