Retinoids are a class of molecules derived from or similar to vitamin A, which is also known as retinol. Retinoids bind to retinoic acid receptors to affect a variety of cellular processes, such as cell differentiation and growth.1 While best known for their aesthetic uses, retinoids are also critical for certain medical needs.
Topical retinoids are a mainstay of cosmetics and dermatology. Specifically, retinol-containing compounds are used to treat acne, skin pigmentation, and skin wrinkles. There are several mechanisms by which retinoids have these effects on skin. Acne occurs when abnormal desquamation – the process of skin being shed – leads to the obstruction of sebaceous glands, the gland in the skin that releases oil and opens into hair.2 Inflammation and excess sebum production can also lead to acne. Topical retinoids such as tretinoin and adapalene reduce acne by lowering desquamation, specifically by reducing the proliferation of certain cells.3 These medications also suppress the production of certain proteins involved in the inflammation pathway.
Dermatologists recommend retinoids for wrinkle treatment and other aesthetic concerns. Retinoids increase the production of collagen and improve skin color by stimulating the production of new blood vessels in cells.4 In one study, 32 women with photodamaged skin were treated with a retinol containing compound called tretinoin.5 After 4 weeks, improvements in fine wrinkles, skin roughness, and hyperpigmentation were observed. Significantly, while the subjects at first did experience some of the typical side effects of retinoids, like dryness, irritation, sensitivity to sunlight, and swelling, on the whole they did not experience these adverse effects after 2 weeks of treatment, which may indicate that retinoid-induced side effects do not persist.
In addition to their aesthetic uses, retinoids also have significant medical applications, especially in cancer treatment. Retinoids are a promising treatment for cancer because they affect the fate of cells via a number of different mechanisms. They influence cell differentiation and proliferation, and have been observed to arrest tumor development and induce apoptosis (programmed cell death) in cancer cells.6 Cancer cells can arise when they acquire mutations in genes related to the regulation of the cell cycle, which prevents cells from growing uncontrollably or experiencing errors in chromosome division. Retinoids can inhibit the progression of cells through the cell cycle, which can prevent these adverse outcomes.7
However, implementing retinoid therapy for cancer is not guaranteed to be effective due to retinoid resistance. This refers to the lack of a tumor cell response to doses of retinoid treatment that are effective in normal cells.8 In some forms of acute promyelocytic leukemia, a type of blood cancer, proteins involved in retinoid signaling pathways lose their ability to respond to retinoids.9 Retinoid resistance has also been documented in carcinomas, cancers in the epithelial tissue, which occurs because certain receptors for retinoic acid are repressed.6 It is suspected that a combination of retinoids with drugs that circumvent these resistance mechanisms could be effective, but studies are needed to confirm this hypothesis. Regardless, retinoids will remain a mainstay of dermatological treatment and a promising agent in cancer treatment for the foreseeable future.
References
1. Motamedi, M., Chehade, A., Sanghera, R. & Grewal, P. A Clinician’s Guide to Topical Retinoids. J. Cutan. Med. Surg. 26, 71–78 (2022), DOI: 10.1177/12034754211035091
2. Gollnick, H. P. et al. A consensus-based practical and daily guide for the treatment of acne patients. J. Eur. Acad. Dermatol. Venereol. JEADV 30, 1480–1490 (2016), DOI: 10.1111/jdv.13675
3. Leyden, J., Stein-Gold, L. & Weiss, J. Why Topical Retinoids Are Mainstay of Therapy for Acne. Dermatol. Ther. 7, 293–304 (2017), DOI: 10.1007/s13555-017-0185-2
4. Do retinoids really reduce wrinkles? Harvard Health https://www.health.harvard.edu/staying-healthy/do-retinoids-really-reduce-wrinkles (2017).
5. Kligman, D. E. & Draelos, Z. D. High-strength tretinoin for rapid retinization of photoaged facial skin. Dermatol. Surg. Off. Publ. Am. Soc. Dermatol. Surg. Al 30, 864–866 (2004), DOI: 10.1111/j.1524-4725.2004.30254
6. Altucci, L. & Gronemeyer, H. The promise of retinoids to fight against cancer. Nat. Rev. Cancer 1, 181–193 (2001), DOI:10.1038/35106036
7. Tang, X.-H. & Gudas, L. J. Retinoids, Retinoic Acid Receptors, and Cancer. Annu. Rev. Pathol. Mech. Dis. 6, 345–364 (2011), DOI: 10.1146/annurev-pathol-011110-130303
8. Freemantle, S. J., Spinella, M. J. & Dmitrovsky, E. Retinoids in cancer therapy and chemoprevention: promise meets resistance. Oncogene 22, 7305–7315 (2003), DOI:10.1038/sj.onc.1206936
9. Zhou, D.-C. et al. Frequent mutations in the ligand-binding domain of PML-RARalpha after multiple relapses of acute promyelocytic leukemia: analysis for functional relationship to response to all-trans retinoic acid and histone deacetylase inhibitors in vitro and in vivo. Blood 99, 1356–1363 (2002), DOI: 10.1182/blood.v99.4.1356