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The general focus of our translational research is the discovery and validation of predictive biomarkers to guide treatment in head and neck cancer.
Despite some advances in the treatment within the last couple of years head and neck cancer remains a devastating disease with limited survival in the recurrent/metastatic situation. Therefore, novel treatment targets, new drug combinations and patient individualized treatment approaches are needed.
Through a close collaboration with epo GmbH we established the largest head and neck cancer xenograft platform in europe. Those PDX are employed for clinically relevant research questions and mimicry of clinical trials.
Validation of preclinical findings are performed in retrospective as well as prospective clinical trials populations within our institution. Recently we focused on the predictive and prognostic role of molecular subtypes of head and neck cancer based on gene expression profiles.
Figure1: The graph displays the head and neck cancer platform comprising 66 extensively characterized models resembling the heterogeneity of the disease. Clinical data are collected for all established models. Furthermore, drug and radiation screening is done for all models to establish basic sensitivity profiles for standard of care compounds. Mutational profiles, gene expression analysis and proteomic and phospho-proteomic profiles complement the tumor profiling.
- Klinghammer K, Keller J, George J, Hoffmann J, Chan EL, Hayman MJ. A phosphoarray platform is capable of personalizing kinase inhibitor therapy in head and neck cancers. Int J Cancer. 2018
- Klinghammer K, Otto R, Raguse JD, Albers AE, Tinhofer I, Fichtner I, Leser U, Keilholz U, Hoffmann J. Basal subtype is predictive for response to cetuximab treatment in patient derived xenografts of squamous cell head and neck cancer, Int Journal of Cancer. 2017
- Klinghammer K, Raguse JD, Plath T, Albers AE, Joehrens K, Zakarneh A, Brzezicha B, Wulf-Goldenberg A, Keilholz U, Hoffmann J, Fichtner I.A comprehensively characterized large panel of head and neck cancer patient-derived xenografts identifies the mTOR inhibitor everolimus as potential new treatment option. Int Journal of Cancer. 2014
- Tinhofer I, Klinghammer K, Weichert W, Knodler M, Stenzinger A, Gauler T, et al. Expression of amphiregulin and EGFRvIII affect outcome of patients with squamous cell carcinoma of the head and neck receiving cetuximab-docetaxel treatment. Clinical cancer research 2011.
- Klinghammer K, Knodler M, Schmittel A, Budach V, Keilholz U, Tinhofer I. Association of epidermal growth factor receptor polymorphism, skin toxicity, and outcome in patients with squamous cell carcinoma of the head and neck receiving cetuximab-docetaxel treatment. Clinical cancer research 2010.
- Rieke DT, Ochsenreither S, Klinghammer K, Seiwert TY, Klauschen F, Tinhofer I, Keilholz U. Methylation of RAD51B, XRCC3 and other homologous recombination genes is associated with expression of immune checkpoints and an inflammatory signature in squamous cell carcinoma of the head and neck, lung and cervix. Oncotarget. 2016
- Klinghammer K, Walther W, Hoffmann J Choosing wisely – Preclinical test models in the era of precision medicine. Cancer Treatment Reviews. 2017
- Klinghammer, K. Malignome des Kopf-Hals Bereichs, Facharztwissen Hämatologie Onkologie, Elsevierverlag 2017