NIH R01 · 2024
Mechanisms of Parp inhibitor-induced bone marrow toxicities
PROJECT SUMMARY Poly-(ADP ribose) polymerase (PARP) inhibitors as a drug class are considered one of the great success stories of Precision Medicine with Food and Drug Administration drug approvals accumulating for growing proportions of patients with diverse cancer types. As well, preclinical studies are investigating their use in a multitude of non-malignant diseases. These drugs inhibit multiple PARP enzymes at once, some of which are critical enzymes for sensing and coordinating repair of several types of DNA damage. Further, these drugs trap the PARP1 enzyme onto DNA, resulting in a DNA double strand break to resolve this lesion. Thus, by design, these drugs increase DNA damage in…
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