DNA Replication Stress
DNA replication is a tightly controlled process
DNA replication in normal cells is tightly regulated to accurately copy the DNA and duplicate the genome. Timing and accuracy are important to ensure a coordinated and efficient replication process to avoid copying errors which may disrupt cell function and contribute to disease.
DNA replication stress is a hallmark of cancer
In cancer, activating mutations in pro-proliferative genes (oncogenes) and inactivating mutations in anti-proliferative genes (tumor suppressor genes) perturb the coordinated replication process, forcing the cancer cells to copy their DNA in an unscheduled premature manner. This phenomenon is a common characteristic of cancer and termed DNA replication stress. It results in the generation of high levels of DNA damage that is continuously repaired by the cancer cell to ensure unrestrained growth.
Targeting DNA replication stress to treat cancer
Cancer strongly depends on DNA repair pathways to cope with DNA replication stress-induced DNA damage. By inhibiting pivotal components of distinct cancer-relevant DNA repair pathways, we aim to selectively target tumor cells while sparing normal cells. We have developed FORX-428, a potent and selective inhibitor of poly (ADP-ribose) glycohydrolase (PARG), a key enzyme in the repair process. FORX-428 is the lead program of FoRx and is currently being investigated in a phase 1 clinical trial.
References
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