Epigenetic targeting in oral squamous cell carcinoma: mechanisms, therapies, and translational potential.

INTRODUCTION

Oral squamous cell carcinoma (OSCC) is a heterogeneous malignancy with rapid progression, limited therapeutic options, and poor prognosis. Epigenetic alterations - including DNA methylation, histone modifications, and noncoding RNA (ncRNA) regulation - are key drivers of oncogene activation and tumor suppressor silencing, offering novel therapeutic opportunities.

AREAS COVERED: This review summarizes the major epigenetic mechanisms in OSCC and highlights recent progress in therapeutic agents and molecular targets. In particular, we emphasize ncRNA-based modulators, such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), which play crucial roles in epigenetic regulation and represent promising therapeutic candidates. Innovative delivery strategies, including exosome-mediated transfer and nanoparticle formulations, are discussed for their potential to improve treatment specificity and overcome resistance. An updated summary of clinical trials targeting epigenetic regulators in OSCC is also presented, along with possible combination strategies to enhance clinical outcomes.

EXPERT COMMENTARY: Epigenetic therapies hold significant promise for precision treatment of OSCC. Combining targeted agents with advanced delivery systems may accelerate clinical translation, while validated biomarkers could support early detection, risk stratification, and personalized therapy.A literature search was conducted in PubMed and ClinicalTrials.gov from January 2002 to July 2025 to identify high-quality studies on epigenetic therapies in OSCC.