Genomic instability represents a hallmark in carcinogenesis and is also intimately linked to cancer therapy, as many conventional treatments, such as ionizing radiation or chemotherapeutics act by means of their DNA-damaging properties. The cancer “mutanome” has been identified as a predictive marker for response in the context of targeted cancer immunotherapy (i.e. checkpoint inhibitor therapy or vaccinations). Research in the field of genomic instability and DNA repair has been a long-standing core area at the UCT Mainz, which was further strengthened by the foundation of the Institute of Molecular Biology (IMB) at the Johannes Gutenberg University. Tumor mutational burden, neoantigens, copy number alterations or small fusions are linked to the core area Cancer Immunotherapy, providing a strong rationale for collaborative efforts.
The major aim of the UCT Mainz program Genetic Instability & Resistance is to develop novel and rationale combination therapies in close collaborations with the core area Cancer Immunotherapy. Further, an IIT-concept to target DNA repair in KRASmut lung cancer patients is under evaluation.
Deng, S., Yan, T., Nikolova, T., Fuhrmann, D., Nemecek, A., Gödtel-Armbrust, U., Kaina, B., Wojnowski, L. 2015. The catalytic topoisomerase II inhibitor dexrazoxane induces DNA breaks, ATF3 and the DNA damage response in cancer cells. Br J Pharmacol. 172(9), 2246-2257.