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

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.

Distinct retinoic gene signatures discriminate Merkel cell polyomavirus‐positive from ‐negative Merkel cell carcinoma cells

“…Likely, a dysregulated retinoic signature might confer a high invasive/transformative potential to MCCP. The results of the present study might open the way to novel retinoid‐based MCC therapies 8 …”

“…Retinoid responses are mediated by different classes of nuclear receptors, whose signaling activation modulates genes that control morphogenesis, development, and homeostasis 5,7 . Retinoic signaling is dysregulated in carcinoma and components of this pathway are reliable antitumor targets, even for managing cutaneous neoplasms 8 . The impairment of development regulators such as SOX2 and the Hedgehog gene family member SHH has been documented in MCC 5,7 .…”

“…5,7 Retinoic signaling is dysregulated in carcinoma and components of this pathway are reliable antitumor targets, even for managing cutaneous neoplasms. 8 The impairment of development regulators such as SOX2 and the Hedgehog gene family member SHH has been documented in MCC. 5,7 In particular, SOX2, regulates the embryonic neural crest stem cell maintenance of the Merkel cell lineage, while being reported as expressed in MCC.…”

Atypical Fibroxanthoma Treated with a Topical Combination of Imiquimod, Tazarotene, and 5-Fluorouracil

“…This process is primarily facilitated through the transcriptional upregulation of p73 , a homolog of p53 , a well-known tumor suppressor gene that plays a significant role in the apoptotic pathway and cellular response to DNA damage [ 31 ]. This mechanism highlights the potential therapeutic applications of tazarotene in targeting abnormal proliferation, particularly relevant in skin cancer treatment and prevention [ 32 ].…”

Recent Advances in Clinical Research for Skin Cancer Chemoprevention

“…Since the retinoid signaling pathway plays an important role in organ homeostasis and carcinogenesis, the natural and synthetic vitamin A derivatives, retinoids, may be effective for the prevention and the treatment of several types of cancer, including skin cancer (for review, see [61]). Initially, oral retinoids demonstrated efficacy as chemopreventive agents against NMSC and other types of cancer [24,48].…”