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Leaders at Artios explore the potential of expanding therapeutic opportunities in DDR beyond synthetic lethality

| Media coverage

Cancer often develops or becomes aggressive because of genomic instability that arises from mutations or aberrations in DNA. These lead to uncontrolled growth, proliferation, and metastatic spread of tumorigenic cells. The body employs a highly sophisticated and coordinated cellular network focused on preserving DNA integrity during states of cell replication or damage, known as the DNA damage response (DDR), designed to prevent the replication of cells with faulty DNA by either repairing the damage or triggering cell death.

Exploiting this inherent genomic protection is a therapeutic area that presents a challenging target for two main reasons. First, the multitude of enzymes important in the DDR have substantially different mechanisms of action to kinases, which have been the primary focus of most druggable targets in cancer cell biology. DDR targets include nucleases, helicases, and polymerases, which contain structural elements that are less characterized and accessible to drugging and therefore require novel mechanistic classes of drugs. A second challenge stems from initial concerns surrounding the blocking mechanisms that repair DNA damage in cells. These may inadvertently induce toxicity in normal cells, which raises the question of whether DNA repair systems that emerge selectively or are upregulated in cancer cells can be targeted to avoid impact on normal cells while specifically affecting cancer cells.


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