forschung hno innsbruck12




  • Predicitve biomarkers
  • Therapy resistance in head and neck cancer
  • Epithelial-mesenchymale transition
  • Tumor-stroma interaction
  • Tumor microenvironment
  • Extracellular vesicles
  • Liquid biopsy
  • Salvage surgery

Approximately one third of all head and neck cancer patients at the Department of Otorhinolaryngology, Medical University of Innsbruck, are treated with first-line radiochemotherapy, especially with cisplatin. One fourth of these patients does not completely respond to first-line therapy. Patients with failure to radiochemotherapy can often be only offered rescue surgery as curative approach, which is associated with a high complication rate and permanent functional impairment. Additionally, patients with progressive disease after first-line therapy frequently presented with distant metastasis, further limiting curative treatment options. These data highlight the relevance of predicitive markers for radiochemotherapy resistance in head and neck cancer and the necessitiy of identifying molecular mechanism of therapy resistance to further improve patient outcome.

This study group focuses on clinical aspects of therapy failure, like the outcomes of salvage surgery but also on preclinical models analysing therapy resistance especially in the context of tumor stroma interaction and epithelial mesenchymal transition (EMT) as one major cause of radiochemotherapy resistance in head and neck cancer. EMT can be mimicked in vitro by co-cultivation of epithelial head and neck cancer cells and tumor-associated fibroblasts. EMT induced cisplatin and radiotherapy resistance of the cancer cells by the induction of anti-apoptotic signalling and increased DNA repair capacities. Furthermore, it increased migrational properties of the cancer cells and led to the induction of a mesenchymal phenotype (EMT). EMT can be assessed in HNC tumor probes by cytokeratin/vimentin co-expression and loss of E-cadherin/β-catenin co-expression. Slug immunohistochemistry was demonstrated to be a convenient surrogate marker for EMT. Consequently, Slug was introduced into our clinical routine immunohistochemical staining of tissue biopsies. Slug-positive patients had a 3.3 times better chance of survival when treated with upfront surgery ± radiotherapy versus primary radiochemotherapy in a multivariable Cox model (p = 0.017). For HNSCC patients, Slug IHC represents a novel and feasible predictive biomarker to support upfront surgery. Additionally, primary radiochemotherapy showed inferior response rates (univariate odds ratio (OR) for treatment failure, 3.6; 95% CI, 1.7 to 7.9; p = 0.001) and inferior 5-year OS (univariate, p < 0.001) in Slug-positive patients. 

Future perspectives include the identification of mediators of therapy resistance in EMT. As our in vitro model of EMT consists of a cell-free conditioned medium we suggest that either soluble signalling-factors or extracellular vesicles might be responsible for the observed effects of co-culture conditioned media. Exosomes are membranous vesicles with a diameter ranging from 40 to 100 nm and are constitutively released by almost all cell types, and mediate cell-to-cell communication by transferring mRNAs, miRNAs, DNAs and proteins causing extrinsic therapy resistance. Especially cancer cells secret high levels of exosomes (32). They transfer therapy resistance by anti-apoptotic signalling, increased DNA-repair or delivering ABC transporters to drug sensitive cells. As functional mediators of tumor-stroma interaction and of EMT, exosomes also promote environment-mediated therapy resistance. Extracellular vesicles are currently isolated from co-culture conditioned medium and analysed in more detail for their protein content. They could also be isolated from the blood of head and neck cancer patients in the context of liquid biopsy in the future.



  • Ira-Ida Skvortsova, Prof.Dr.,
  • Dragana Savic
  • Department of Therapeutic Radiology and Oncology
  • Medical University of Innsbruck 
  • Herbert Linder, Prof., PhD, Bettina Sarg, PD; Dr. rer.nat.
  • Biocenter, Division of Clinical Biochemistry
  • Medical University of Innsbruck 
  • European Organisation for. Research and Treatment of Cancer (EORTC)


Steinbichler Teresa Beranadette, PD, Dr.

Dr. Jozsef Dudas, PD, PhD

Mag.rer.nat. Julia Ingruber, PhD

Santer Matthias, Dr.

Herbert Riechelmann (until 2022)


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