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Another ASCO success story is the OlympiAD trial published in NEJM this weekend. Olaparib (a PARPi) improved progression free survival compared to standard chemo in patients with HER2(-), BRCA-mutated metastatic breast cancer. This is an important example of synthetic lethality. To grossly oversimplify (you're welcome), PARP repairs minor but frequent DNA damage. And if PARP doesn't fix things, the big guns (homologous recombination) typically pick up the slack. But, if homologous recombination also doesn't work (as in this case of a BRCA-mutation), all those tiny little problems become big problems. Looks like BRCA-mutated breast cancer's got 99 problems...and PARP inhibition just became a big one.