Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers

摘要: Tumor cells are often deficient in DNA damage response (DDR) pathways, and anticancer therapies commonly based on genotoxic treatments using radiation and/or drugs that directly or interfere with metabolism, leading to the formation of double-strand breaks (DSB), ultimately cell death. Because DSBs induce phosphorylation histone H2AX (γH2AX) chromatin flanking break site, an antibody directed against γH2AX can be employed measure levels before after patient treatment. Poly(ADP-ribose) polymerases (PARP1 PARP2) also activated by damage, PARP inhibitors show promising activity cancers defective homologous recombination (HR) pathways for DSB repair. Ongoing clinical trials testing combinations damaging agents. Poly(ADP-ribosylation), abbreviated as PAR, measured samples used determine efficiency inhibitors. This review summarizes roles PAR DDR, their use biomarkers monitor drug guide trials, especially phase 0 trials. We discuss choices relevant analyses.