MIPS Seminar: Inhibition of Nucleotide Excision Repair by the Anti-Cancer, G-Quadruplex DNA Binding Drug CX-5461

Alexandra Berroyer, PhD, Research Fellow, JBL, HSPH

Drugs that target G-Quadruplex DNA structures are being implemented in cancer therapy and have been shown to effectively kill cancer cells by inducing double-strand DNA breaks. While one G-Quadruplex DNA binding drug called CX-5461 has shown promise in recent clinical trials, patients administered CX-5461 experienced acute UV-photosensitivity indicating CX-5461 treatment may affect the nucleotide excision DNA repair pathway that removes UV- and cisplatin-induced lesions from DNA. The work shared in this presentation identifies CX-5461 as a novel nucleotide excision repair inhibitor that may be able to fulfill the longstanding, unmet need to successfully target the nucleotide excision repair pathway as a mechanism to kill cancer cells.