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Radiobiology of Head and Neck Cancer

PD Dr. Thorsten Rieckmann, Dipl.-Biol.
Dr. Henrike Zech, HNO-Ärztin
Sabrina Christiansen, BTA
Fruzsina Gatzemeier, BTA
Agnes Oetting MSc.Physik PhD Stud.
Ruth Rietow, MSc.MLS PhD Stud

Topic

The main interest of our group is to understand the biological mechanisms of the enhanced radiation sensitivity of HPV (Human Papillomavirus)-induced head and neck cancer. These tumors, which are caused by the same high-risk HPV types that cause cervical cancer and other anogenital malignancies, represent a growing subset of head and neck squamous cell carcinoma (HNSCC) in many countries. We aim to understand the molecular mechanisms responsible for the favorable outcome of patients with HPV-positive HNSCC and to use this knowedge for the establishment of specific therapeutic approaches in order to safely de-intensify treatment and reduce toxicities. Our resarch focusses on the enhanced intrinsic cellular radiation sensitivity caused by a defect in the repair of radiotherapy induced DNA double-strand breaks and specific ways to target the functional components of the DNA damage response and double-strand break repair, such as PARP1 and the cell cycle checkpoint kinases Chk1 and Wee1 in various model systems, such as cell lines, patient derived xenografts and tumor slice cultures.

Funding

Deutsche Forschungsgesellschaft, Deutsche Krebshilfe, BMBF, Brigitte und Dr. Konstanze Wegener-Stiftung, Roggenbuck Stiftung

Selected Publications

  • Improving the Efficacy of Tumor Radiosensitization Through Combined Molecular Targeting. Hintelmann K, Kriegs M, Rothkamm K, Rieckmann T. Front. Oncol. 2020 10:1260
  • Mass Spectrometric Comparison of HPV-Positive and HPV-Negative Oropharyngeal Cancer. Wurlitzer M, Möckelmann N, Kriegs M, Vens M, Omidi M, Hoffer K, Bargen CV, Möller-Koop C, Witt M, Droste C, Oetting A, Petersen H, Busch CJ, Münscher A, Schlüter H, Clauditz TS, Rieckmann T. Cancers (Basel). 2020 Jun 11;12(6):1531.
  • Dual PI3K/mTOR Inhibitor NVP-BEZ235 Enhances Radiosensitivity of Head and Neck Squamous Cell Carcinoma (HNSCC) Cell Lines Due to Suppressed Double-Strand Break (DSB) Repair by Non-Homologous End Joining. Schötz U, Balzer V, Brandt FW, Ziemann F, Subtil FSB, Rieckmann T, Köcher S, Engenhart-Cabillic R, Dikomey E, Wittig A, Arenz A.. Cancers (Basel). 2020 Feb 18;12(2):467.
  • The failure of cetuximab-based de-intensified regimes for HPV-positive OPSCC: A radiobiologists perspective. Rieckmann T, Kriegs M. Clin Transl Radiat Oncol. 2019 May 22;17:47-50.
  • Modulation of radiation sensitivity and antitumor immunity by viral pathogenic factors: Implications for radio-immunotherapy. Franz Rödel, Daniel Martin, Panagiotis Balermpas, Ulrike Wieland, Ria Winkelmann, Thorsten Rieckmann, Stephan Falk, Claus Rödel, Emmanouil Fokas. Biochim Biophys Acta Rev Cancer 2019 Jan;1871(1):126-137.
  • Roscovitine strongly enhances the effect of olaparib on radiosensitivity for HPV neg. but not for HPV pos. HNSCC cell lines. Ziemann F, Seltzsam S, Dreffke K, Preising S, Arenz A, Subtil FSB, Rieckmann T, Engenhart-Cabillic R, Dikomey E, Wittig A. Oncotarget. 2017 Oct 24;8(62):105170-105183
  • G2-checkpoint targeting and radiosensitization of HPV/p16-positive HNSCC cells through the inhibition of Chk1 and Wee1. Busch CJ, Kröger MS, Jensen J, Kriegs M, Gatzemeier F, Petersen C, Münscher A, Rothkamm K, Rieckmann T. Radiother Oncol. 2017 Feb;122(2):260-266
  • Similar cisplatin sensitivity of HPV-positive and -negative HNSCC cell lines. Busch CJ, Becker B, Kriegs M, Gatzemeier F, Krüger K, Möckelmann N, Fritz G, Petersen C, Knecht R, Rothkamm K, Rieckmann T. Oncotarget. 2016 Jun 14;7(24):35832-35842
  • HPV and Radiation Sensitivity. De Costa AM, Rieckmann T, Kimple R J. Human Papillomavirus (HPV)-Associated Oropharyngeal Cancer. 1st Edition. 2015, Chapter 12, Page 243-289, Springer International Publishing
  • The inhibition of PARP but not EGFR results in the radiosensitization of HPV/p16-positive HNSCC cell lines. Güster JD, Weissleder SV, Busch CJ, Kriegs M, Petersen C, Knecht R, Dikomey E, Rieckmann T. Radiother Oncol; 2014,13(3):345-51.
  • HPV-positive HNSCC cell lines but not primary human fibroblasts are radiosensitized by the inhibition of Chk1. Busch CJ, Kriegs M, Laban S, Tribius S, Knecht R, Petersen C, Dikomey E, Rieckmann T. Radiother Oncol; 2013, Sep, 108(3):495-9.
  • HNSCC cell lines positive for HPV and p16 possess higher cellular radiosensitivity due to an impaired DSB repair capacity. Rieckmann T, Tribius S, Grob TJ, Meyer F, Busch CJ, Petersen C, Dikomey E, Kriegs M. Radiother Oncol; 2013, 107(2):242-6.