Identification of Biomarkers Influencing Treatment Response and Clinical Prognosis in Head and Neck Cancer

Head neck

We aim to study the signaling pathways involved in response/resistance to cisplatin, cetuximab, and radiotherapy in order to find new predictive markers and new targets for therapy

Cancer of the head and neck is the sixth most common form of cancer worldwide with about 1300 new cases per year in Sweden. The majority of all head and neck cancers are squamous cell carcinomas (HNSCC) having their origin in the mucosa of the oral cavity, pharynx, larynx, and nasal cavity.

Despite advances in surgical and oncological treatments that enhance quality of life with a palliative value, the overall survival rate has significantly not increased. A combination of radiotherapy and surgery or definitive chemoradiation is currently the primary mode of treatment for locally advanced HNSCC. Moreover, a monoclonal antibody against the epidermal growth factor receptor (EGFR), cetuximab (Erbitux®), has been approved for the treatment of advanced HNSCC.

HNSCC often show resistance to treatments and the 5-year survival rate is merely 50%. Thus there is a paramount need for assessment of predictive biomarkers and new targets for treatment. Due to the limited predictive value of the currently available biomarkers currently available for guiding treatment recommendations, both under- and over treatment occur, with significant suffering and socio-economic waste as a result. In this project, patient tumor biopsies, HNSCC cell lines that we have established from the tumor biopsies and mice xenografts obtained from these cell lines are used for evaluation of therapies and characterization of tumor cell properties.

The main aim of these studies is to identify biomarkers that influence the response of tumors to anti-cancer therapy. Such factors may be useful predictors of treatment response and valuable tools in the development of personalized medicine. Ideally, these factors are also targetable, providing possibilities for the development of novel therapies.

Specifically we aim to

  • Study the signaling pathways involved in response/resistance to cisplatin, cetuximab, and radiotherapy in order to find new predictive markers and new targets for therapy.
  • Investigate the role of epithelial-to-mesenchymal transition (EMT) and cancer stem cells (CSC), their connection to each other and to hypoxia and their impact on the outcome of the therapy in HNSCC.
  • Evaluate the importance of survivin and WRAP53β expression for the treatment outcome in a unique patient cohort.

Clinical application/relevance

Despite advances in surgical and oncological treatments, the overall survival of HNSCC patients has not improved significantly in recent years. There is an urgent need for better markers of treatment response and novel targets for therapeutic interventions. T

he ultimate aim of our project is to identify biomarkers for treatment response that also are targetable, potentially leading to future novel therapies. We have established a unique collection of tumor biopsies and tumor cell lines and our approach combining patient material – cell culture – and xenograft models provides the tools necessary to achieve our objectives.

Our hope is that by developing targeted, individualized therapy for HNSCC patients, survival rates will increase, individual quality of life will improve, and resources will be used more economically. Although the focus of this study is HNSCC, many cancers share basic mechanisms, and it is therefore possible that our results may prove to be applicable in guiding treatment of a broad range of solid tumors.