The new study showed that AOH1996 kills cancer cells by disrupting the cell reproductive cycle, specifically inhibiting transcription-replication conflicts—a phenomenon that occurs when the cell machinery responsible for genome duplication and gene expression literally run into each other on the spot in the genome. This leads to DNA replication stress, genomic instability and, ultimately, can give rise to cancer.
By targeting mutated PCNA with AOH1996, the researchers kept cells with damaged DNA from dividing while leaving normal cells intact, as shown by studies of the drug’s effects on healthy stem cells