Epigenetics and Cutaneous Neoplasms: From Mechanism to Therapy

Abstract

Epigenetics encompasses heritable, reversible gene expression patterns that do not arise from mutations in genomic DNA but, rather, are regulated by DNA methylation, histone modifications, RNA modifications and ncRNAs; and epigenetic dysregulation is increasingly recognized as a mechanism of neoplastic disease progression as well as resistance to cancer therapy. This review article focuses on epigenetic modifications implicated in the progression and therapeutic resistance of common cutaneous malignancies, including basal cell carcinoma, squamous cell carcinoma, T-cell lymphoma and malignant melanoma, with an emphasis on therapeutic strategies that may be used to target such disease-associated alterations.

Plain language summary

Epigenetics involves the study of how genes can be turned on or off by factors that affect how these genes are packaged and regulated. In cancer, there are often epigenetic changes that contribute to the formation of tumors. Many of these epigenetic changes, some of which can be passed down through generations, increase the risk of skin cancers such as basal cell carcinoma, squamous cell carcinoma, T-cell lymphoma and malignant melanoma. Emerging therapies designed to target these epigenetic changes may be effective treatments for these types of skin cancers. Researchers are currently investigating how to best use these therapies to help the ever-increasing number of people with skin cancer.

Tweetable abstract

Read the authors’ recent review from Gibson et al. describing how #epigenetic modifications drive cutaneous neoplasms from #melanoma and #BCC to #cSCC and #CTCL. These noncoding events have become of particular interest as therapeutic targets and are being leveraged in clinical trials.

Keywords::

• BCC
• cSCC
• CTCL
• DNA methylation
• epigenetics
• histone
• melanoma
• ncRNA
• skin cancer

R Alani, M Collard, F Gibson, A Hanly and M Wu contributed to the concepts of the review; F Gibson, A Hanly, R Fisher, WA Wyant and M Collard performed the literature search and drafted the review; all authors contributed to the editing phase of the review.

Financial & competing interests disclosure

R Alani is supported by a Department of Defense Translational Research Award in Melanoma (W81XWH-21-1-0980); M Collard is supported by an MRA Dermatology Fellows Award (https://doi.org/10.48050/pc.gr.147045) and a Department of Defense Translational Research Award in Melanoma (W81XWH-21-1-0980). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

R Alani is supported by a Department of Defense Translational Research Award in Melanoma (W81XWH-21-1-0980); M Collard is supported by an MRA Dermatology Fellows Award (https://doi.org/10.48050/pc.gr.147045) and a Department of Defense Translational Research Award in Melanoma (W81XWH-21-1-0980). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.