Research Group Molecular Mechanisms of Head and Neck Tumors

Head and neck cancer is one of the most frequent and dismal human malignancies with so far limited therapeutic options. The majority represents squamous cell carcinoma (HNSCC) arising from the epithelium lining the sinonasal tract, oral cavity, pharynx and larynx. HNSCC has long been a treatment challenge due to the high rate of recurrence and local metastasis. Hence, the identification for novel prognostic biomarkers to objectively predict patients with high risk for tumor relapse and the development of more effective and less toxic treatment modalities are eagerly awaited. Similar to other solid tumors HNSCC development is a complex multistep process characterized by the accumulation of genetic and epigenetic alteration. Our research program is based on functional genomic and proteome analyses as well as experimental studies using human tumor samples, preclinical mouse tumor models and cell lines derived thereof, and focuses on: (i) topological characteristics of signaling and gene regulatory networks in the pathogenesis of HNSCC, (ii) molecular mechanisms underlying the establishment and maintenance of tumor recurrence, and (iii) the role of the pro-inflammatory microenvironment in HNSCC. The major aim of our studies is the identification of novel molecular biomarkers and putative drug targets for translational cancer research.

Although the principle risk factors for HNSCC remain tobacco and alcohol use, human papilloma virus infection has recently been found to be etiologically associated with 20-25% of HNSCC, espacially in the oropharynx. Strikingly, the majority of HNSCC patients harboring HPV-positive carcinomas presents with an advanced stage of the disease at the time of diagnose; however, there is growing evidence that these patients have a favorable prognosis independent of the therapeutic treatment regimen. We propose that a systematic analysis of HPV-negative and HPV-positive oropharyngeal squamous cell carcinomas will not only enhance our knowledge on the impact of HPV infection on neoplastic transformation, but could also improve strategies of cancer prevention and therapy. Tumor development and progression is not driven exclusively by the accumulation of genetic and epigenetic changes in cancer cells, but rather requires a permissive and supportive tumor microenvironment, which may be favored by chronic inflammation, a state often preceding the development of cancer. Indeed, numerous studies demonstrated that most HNSCCs are highly inflammatory in nature and express a plethora of pro-inflammatory mediators. In order to address the impact of an inflammatory microenvironment on the pathogenesis of HNSCC and to proof the concept whether pharmaceutical targeting of inflammation serves as an innovative option for tumor prevention or therapy, we will continue to establish and investigate preclinical mouse tumor models.