Medicine and Health Sciences Commons^™

Sprtn Metalloprotease As A Target To Sensitize Cancer Cells To Crosslinking Chemotherapy, Cole J. Turner

Honors Theses

Bifunctional alkylating agents have demonstrated high clinical utility as a chemotherapeutic strategy against cancer. These compounds have been well-characterized for their capacity to exert cytotoxicity via interstrand DNA crosslinking. However, the same electrophilic chemistry can also form DNA-protein crosslinks (DPCs) whose contributions to these drugs’ antitumor effects have been less well-defined. Recently, the metalloprotease SPRTN has been implicated as a predominant mediator of DPC repair in mammalian cells. Previous work has demonstrated that SPRTN deficiency increases the sensitivity of cancer cells to DPC-inducing agents such as formaldehyde and cisplatin, but these findings have yet to be translated more broadly across …