Header Forschung

Biomarkers for stratification of patients with head and neck squamous cell carcinoma (HNSCC)

Summary of the Project

This interdisciplinary project evaluates potential biomarkers that may later be used for stratification of patients with head and neck squamous cell carcinoma (HNSCC).

Previous data generated within a Joint Funding project of the German Cancer Consortium (DKTK) have shown for the first time that patients with HPV-positive locally advanced HNSCC and postoperative radiochemotherapy have a nearly 100% locoregional tumour control rate over 5 years. Tumours with particularly unfavorable outcome were characterized by e.g. high cancer stem cell marker expression and high hypoxia induced gene expression within the surgically removed tumour specimen. Cancer stem cell markers and hypoxia-induced gene expression are also able to distinguish favorable and unfavorable outcome groups for primary radiochemotherapy.

The present project adds now a group of patients with early stage HNSCC that received surgery alone. HPV analysis, hypothesis-based gene panel analysis (genes coding for proliferation, invasiveness, cell survival mechanisms or mechanisms of sensitivity or resistance to anti-cancer treatments) and protein expression analysis will be performed in surgical material of those patients in a hypothesis generating and a validation cohort.

This data, together with the existent radiooncological patient group mentioned above, will lead to the completion of a cohort of patients treated for the same tumour entity with different standard treatment modalities. The data will give a unique basis for treatment individualisation strategies.

Scientific Goals

  • Detect biomarkers that can later be used for prospective interventional trials on treatment individualization.
  • Generate a prospective clinical protocol that utilizes the established biomarkers for stratification of patients in order to personalize treatment of HNSCC.
HNSCC Picture

Kaplan–Meier estimates of locoregional tumour control of the putative cancer stem cell markers CD44 and SLC3A2. Patients with HPV-negative HNSCC with high CD44 protein or SLC3A2 gene expression showed unfavourable locoregional tumor control compared with patients with little or no cancer stem cell marker expression. @Linge, Baumann, Krause et al.

Linge A, Löck S, Gudziol V, Nowak A, Lohaus F, von Neubeck C, Jütz M, Abdollahi A, Debus J, Tinhofer I, Budach V, Sak A, Stuschke M, Balermpas P, Rödel C, Avlar M, Grosu AL, Bayer C, Belka C, Pigorsch S, Combs SE, Welz S, Zips D, Buchholz F, Aust DE, Baretton GB, Thames HD, Dubrovska A, Alsner J, Overgaard J, Baumann M, Krause M for the DKTK-ROG (2015)
Low CSC marker expression and low hypoxia-induced gene expression identify good prognosis subgroups in HPV(-) HNSCC after postoperative radiochemotherapy. Clin Cancer Res 22, 2639-49

Lohaus F, Linge A (joint first authorship), Tinhofer I, Budach V, Gkika E, Stuschke M, Balermpas P, Rödel C, Avlar M, Grosu AL, Abdollahi A, Debus J, Bayer C, Belka C, Pigorsch S, Combs SE, Mönnich D, Zips D, von Neubeck C, Baretton GB, Löck S, Thames HD, Krause M, Baumann M for the DKTK-ROG (2014) HPV16 DNA status is a strong prognosticator of loco-regional control after postoperative radiochemotherapy of locally advanced oropharyngeal carcinoma: Results from a multicentre explorative study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG). Radiother Oncol 113, 317-23

Koch U, Höhne K, von Neubeck C, Thames HD, Yaromina A, Dahm-Daphi J, Baumann M, Krause M (2013) Residual gH2AX foci predict local tumour control after radiotherapy. Radiother Oncol 108, 434-39

Soliman M, Yaromina A, Appold S, Zips D, Reiffenstuhl C, Schreiber A, Thames HD, Krause M, Baumann M (2013) GTV differentially impacts locoregional control of non-small cell lung cancer (NSCLC) after different fractionation schedules: Subgroup analysis of the prospective randomized CHARTWEL trial. Radiother Oncol 106, 229-304

Krause M, Yaromina A, Eicheler W, Koch U, Baumann M (2011) Cancer stem cells: targets and potential biomarkers for radiotherapy. Clin Cancer Res 17, 7224-29

Contact

Prof. Mechthild Krause
Director, Dept. of Radiation Oncology, University Hospital Carl Gustav Carus Dresden; Dept. of Radiooncology – OncoRay, Helmholtz-Zentrum Dresden-Rossendorf; OncoRay
Phone: +49 351 458 5441
Email: Mechthild.krause(at)uniklinikum-dresden.de