The Deutsches Krebsforschungszentrum (German Cancer Research Center, DKFZ) is a foundation under public law and a member of the Helmholtz Association of National Research Centers (Helmholtz-Gemeinschaft Deutscher Forschungszentren, HGF). As a national research center (about 1800 employees) it is financed by the Federal German Government and the State of Baden-Wuerttemberg. DKFZ has the task to systematically investigate the mechanisms of cancer development and to identify cancer risk factors. The results of this basic research provide the basis for developing new approaches in the prevention, diagnosis, and treatment of cancer.

Persistent infection with Human papillomaviruses (HPV) is a causal factor for cancer of the cervix and other anogenital sites and for a subgroup of oral cancers. Two virus-encoded oncoproteins, E6 and E7, are continuously expressed in the tumor cells and interfere with regulation of cell cycle and apoptosis through direct interaction with cellular proteins. This project will identify small molecule inhibitors of the interaction HPV type 16 E7 with the human retinoblastoma protein pRB and of E6 with the human proteins E6AP and tumor suppressor p53.

Munoz, N.; Bosch, F. X.; de Sanjose, S.; Herrero, R.; Castellsague, X.; Shah, K. V.; Snijders, P. J.; Meijer, C. J., Epidemiologic classification of human papillomavirus types associated with cervical cancer. N. Engl. J. Med. 2003, 348, 518-527. zur Hausen, H., Papillomaviruses causing cancer: evasion from host-cell control in early events in carcinogenesis. J. Natl. Cancer Inst. 2000, 92, 690-698. Dong, W. L., Caldeira, S., Sehr, P., Pawlita, M., and Tommasino, M. (2001). Determination of the binding affinity of different human papillomavirus E7 proteins for the tumour suppressor pRb by a plate-binding assay. J Virol Methods 98(1), 91-8. Sehr, P., Zumbach, K., and Pawlita, M. (2001). A generic capture ELISA for recombinant proteins fused to glutathione S-transferase: validation for HPV serology. J Immunol Methods 253(1-2), 153-62. Waterboer, T.; Sehr, P.; Michael, K. M.; Franceschi, S.; Nieland, J. D.; Joos, T. O.; Templin, M. F.; Pawlita, M., Multiplex human papillomavirus serology based on in situ-purified glutathione s-transferase fusion proteins. Clin. Chem. 2005, 51, 1845-1853.