Research Projects

Oral cancer is a major global health concern, ranking among the most common malignancies worldwide, with oral squamous cell carcinoma (OSCC) accounting for over 90% of all oral cancers. OSCC arises from the squamous epithelium lining the oral cavity and is characterized by aggressive behavior, high recurrence rates, and significant morbidity and mortality. Despite advances in treatment, the survival rate for OSCC remains low, primarily due to limited understanding of the underlying molecular mechanisms. Importantly, the incidence and mortality rates of OSCC are significantly higher in males than females, a disparity traditionally attributed to lifestyle and environmental factors such as tobacco use, alcohol consumption, and occupational hazards. However, emerging evidence suggests that intrinsic molecular mechanisms, particularly those involving sex hormone signaling, may also contribute to this gender bias. Among these, the androgen receptor (AR) has gained attention as a critical factor influencing OSCC development and progression. Our preliminary findings indicate that AR signaling drives OSCC cell proliferation, likely through chromatin association and interactions with X- and Y-linked genes, suggesting AR as a pivotal player in the molecular pathways underlying OSCC pathogenesis. This highlights the urgent need for a deeper understanding of the role of AR in the disease, particularly in relation to gender-specific differences in incidence and outcomes. The overarching goal of this research is to elucidate the molecular mechanisms by which AR signaling contributes to OSCC progression and to explore novel therapeutic avenues. To achieve this, we will focus on three objectives: first, investigating how AR signaling promotes OSCC proliferation, self-renewal, and tumorigenesis, with particular attention to chromatin modifications and interactions with sex chromosome-linked genes; second, examining the role of AR in tumor-stroma crosstalk, particularly its involvement in the activation of cancer-associated fibroblasts (CAFs), using advanced 3D tumoroid models to mimic the tumor microenvironment of OSCC; and third, developing and validating therapies targeting the AR/sex chromosome regulatory network to disrupt AR-driven pathways. By integrating insights from sex hormone signaling, chromatin biology, and tumor microenvironment dynamics, this study aims to advance the development of gender-specific therapies and improve OSCC outcomes. Ultimately, the research seeks to reduce the global burden of OSCC by providing a deeper understanding of the intricate interplay between AR signaling and OSCC pathogenesis and paving the way for advancements in personalized cancer care.