Therapeutic targets and intervention

The 5-year survival rate of head and neck squamous cell carcinoma (HNSCC) patients after radiotherapy alone or combined with chemo- or immunotherapy is only about 45%. The main reason for the unfavourable survival rate of HNSCC is therapy failure due to resistance of tumours against radiation and hypersensitivity of normal tissue the underlying mechanisms of which are poorly understood. Our research on HNSCC, therefore, focuses on the understanding of the molecular mechanisms governing cellular radiation sensitivity and involves

  • Multi-level (genome, mRNA, miRNA) omics data generation using our in-house Agilent microarray platform and bioinformatics integration of the resulting data (LINK IBG)
  • Validation of previously identified cytogenetic markers for radiation resistance in HNSCC in retro- and prospective studies of well-characterised independent tumour sets
  • Methodological validation of identified markers by FISH, qRT-PCR and IHC
  • HNSCC HPV status analysis
  • Generation and characterisation of HNSCC tumour cell lines or hTERT immortalized normal cells from fresh tissue
  • Establishment of cell culture models with over and under expressed targets for functional characterization of promising candidate genes for radiation sensitivity
  • Cytogenetic characterisation of cell lines and cell culture models
  • Investigation of phenotypic endpoints of radiation sensitivity including long-term survival, viability, chromosomal aberrations, apoptosis, senescence and migration

Our main research aim is the identification of molecular biomarkers predicting radiation sensitivity and candidate molecules for targeted radio-sensitisation in HNSCC. This would allow the adaption of individualised therapeutic radiation doses and the identification of patients who could benefit from alternative personalised therapy approaches, thus optimising radiation therapy in the treatment of HNSCC.

The research group is embedded in the new HMGU Clinical Cooperation Group “Personalized Radiotherapy in Head and Neck Cancer”  in the context of which we combine the findings of our preclinical investigations with clinical research. One of the main aims of the CCG is to validate and to characterise in detail the genes affected by the gains on chromosomes 1 and 6 that we previously identified as cytogenetic markers of radiation resistance in HNSCC (Bauer et al., 2008). This will provide more detailed information on the clinical significance and relevance of DNA gains on chromosomes 1 and 16 and of FancA alterations as biomarkers specific for radiation resistance.