Epigenetic regulatory mechanisms of histone acetylation in the treatment of cutaneous squamous cell carcinoma

Abstract

Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy; as such, novel systemic therapies are important for the treatment of locally advanced or metastatic disease. Histone deacetylase (HDAC) inhibitors have been increasingly studied in recent years as epigenome-targeted therapy for cSCC. HDACs inhibitors reduce tumorigenesis by blocking HDAC activity and creating a more relaxed chromatin structure, thus inducing gene expression by inhibiting deacetylation of transcription factors. In vitro experiments and in vivo mice studies have shown that HDAC inhibition halts cSCC pathogenesis. Ginsenoside 20(R)-Rg3 has been successfully employed to inhibit HDAC3 and thereby inhibit cSCC epithelial mesenchymal transition. Similarly, vorinostat has been found to blunt growth of human xenograft epidermoid cSCCs in highly immunosuppressed mice. Additionally, trichostatin A induces irreversible growth arrest in SCC cells, and MS-275 significantly reduces cSCC tumor burden in mice. These recent studies indicate that HDAC inhibitors represent a promising emerging therapy for cSCC.

KEYWORDS:

• Cutaneous squamous cell carcinomas
• histone deacetylase inhibitors
• tumor epigenetics

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.