Head and Neck Squamous Cell Carcinoma
Head and neck squamous cell carcinoma (HNSCC) is comprised of cancer of the epithelial lining of the mucosal surface inside the head and neck, including the oral cavity, larynx and pharynx. Cancers of the oral cavity and larynx are frequently associated with tobacco and alcohol consumption, while cancers of the pharynx are attributed to HPV exposure. Our work focuses on HPV negative cases, which tend to be more aggressive and metastatic. Treatment of HPV negative HNSCC typically includes surgery, radiation and chemotherapy, as well as targeted therapies including Cetuximab, the monoclonal antibody against EGFR, and Pembrolizumab, a monoclonal antibody against PD-1 on lymphocytes. Despite these treatment options, the 5-year overall survival is below 50%. Ongoing efforts in our lab aim to integrate our understanding of HNSCC, epigenetics and the tumor microenvironment to develop better therapeutic options for patients.
Epigenetics
Epigenetics refers to the study of heritable changes in gene expression that occur without alterations in the underlying DNA sequence. Epigenetic mechanisms include DNA methylation, post-translational modifications to histones, and non-coding RNA, which change the expression of genes. In cancer, these mechanisms can contribute to tumor initiation and progression by enhancing oncogene expression and silencing tumor suppressors. Epigenetic mechanisms make attractive therapeutic targets because unlike genetic mutations, epigenetic changes are reversible. This allows for the potential to restore normal gene expression and cellular function. Our lab focuses on how the altered epigenome in HNSCC leads to change in the tumor microenvironment.
Tumor Microenvironment
The tumor microenvironment (TME) is comprised of the various non-cancer cells that surround the tumor, including immune cells, endothelial cells, and fibroblasts, as well as secreted factors like the extracellular matrix and cytokines. All of these components work together to promote tumor growth, survival, metastasis and drug resistance. A critical component of the TME is the cancer-associated fibroblasts (CAF) population. Our lab focuses on the role of CAFs in shaping the overall TME, and how this alters the epigenome of the tumor cells.