This federal Project Grant award from the National Cancer Institute (NCI), under the Cancer Treatment Research program (CFDA 93.395), is providing $224,100 to the University of Maryland, Baltimore (UMB) to investigate the role of neddylation in repairing replication damage caused by topoisomerase I inhibitors in colorectal cancer.
Specifically, the award aims to: 1) assess the combination of the topoisomerase I inhibitor irinotecan and the neddylation inhibitor pevonedistat in colorectal cancer preclinical models; 2) determine if the CRL4 ubiquitin ligase complex ubiquitylates topoisomerase I-DNA crosslinks and if the DCAF13 protein recruits these crosslinks to CRL4; and 3) examine how neddylation modifies histones and p53 to facilitate the repair of topoisomerase I-induced DNA double-strand breaks. This research is expected to enhance understanding of the mechanisms that allow cancer cells to repair topoisomerase I-targeted DNA damage, with the goal of improving the clinical efficacy of topoisomerase I inhibitors for colorectal cancer treatment.
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