Removing the chromatin remodeler ALC1 sensitized a range of ovarian cancer models to PARP inhibitors while sparing non-cancerous cells, according to new research. The study used endogenous replication-stress measurements—specifically pT21-RPA2—as a predictor of which tumors respond to the ALC1–PARP combination strategy. The findings position ALC1 inhibition as a way to widen the set of tumors likely to respond to PARP therapy, especially in contexts where replication stress is present but actionable vulnerabilities are not fully exploited. Importantly, the paper reports a link between biomarker levels and response, which could help guide patient selection. For clinical translation, the central question is whether pT21-RPA2 (or a feasible surrogate assay) can be measured reliably in patient tumors and whether the therapeutic window holds in diverse histologies and prior-treatment settings.