Understanding tumor progression and therapy resistance in Head and Neck Squamous Cell Carcinomas

• Applicants: Nima Abedpour, Ph.D.; Professorin Dr. Julie George
• Subject Area: Otolaryngology, Phoniatrics and Audiology ; General Genetics and Functional Genome Biology ; Hematology, Oncology ; Cell Biology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 497777992

Head and neck squamous cell carcinomas (HNSCCs) affect worldwide approx. 600.000 patients per year. Surgery and radio-chemotherapy provide initial curative treatment. However, 50% of the patients relapse and die of the disease. Previous profiling studies on single tumors provided insights into the genomic nature of HNSCC. However, the genomic patterns that determine the aggressive growth of tumors, quick relapse and therapy resistance are currently not well understood. An improvement of therapy for HNSCC patients requires a deep understanding of the underlying genomic and molecular mechanisms of tumor progression and therapy resistance. We therefore plan to perform multi-regional and longitudinal genomic profiling (WES, WGS) of patient tumors at the time of diagnosis and at relapse. WES will provide a sequencing depth to study low abundant mutations and intra-tumor heterogeneity. WGS will allow us to capture genomic complexities, as a consequence of tumor progression and therapy. Additional transcriptome sequencing will aid to further our understanding on the expression status and potential on-going events of transcriptional plasticity. Our goal is to provide a comprehensive analysis of therapy resistant tumors, and to thus uncover novel treatment options for patients with HNSCC. We anticipate that this work will shed light on basic aspects of tumor initiation, tumor progression and therapy sensitivity and subsequent resistance, and provide generalizable rationales for the treatment of HNSCC and related cancer types.

• DFG Programme: Research Grants
• Co-Investigators: Professor Dr. Jens Peter Klußmann; Professor Dr. Martin Peifer; Professor Dr. Alexander Quaas