DR-416 Mutational signatures of Topoisomerase I poisons in cancer cell models and human tumours

DNA Topoisomerase 1 (Top1) relieves DNA supercoils. Top1 poisons, such as irinotecan, inhibit Top1 DNA religation activity causing DNA breaks, genome instability and apoptosis, especially in tumour cells. Currently, Irinotecan is indicated for combination regimen of metastatic colorectal cancer patients. Top1 poison-induced DNA damage can be repaired leading to cell survival and cancer cell growth advantages. My project aims at identifying mutational signatures and genomic consequences of Top1 poisons-induced DNA damage and repair in cancers. In particular, I will use Hartwig Medical Foundation datasets to discover mutational signatures associated with Top1 poison treatments in colorectal cancer patients, and their putative correlation with clinical data of patients. The findings can help to develop personalized strategies for patients and to better understand genomic and functonal mechanisms of Top1 poisons in cancers.

Giovanni Capranico, University of Bologna, Italy