Eur J Cancer: HOXA9 meth-ctDNA acts as biomarker for BRCA mutant ovarian cancer

Poly (ADP-ribose) polymerase (PARP) inhibitors have become a new treatment option for BRCA mutationsovarian cancer(OC); Therefore, we studied whether homeobox A9 (HOXA9) promoter methylation in circulating tumor DNA can be treated with PARP inhibitors as a biomarker in patients with platinum-resistant BRCA mutationOCpatients (n s 32) were included as part of a Phase II trial to test veliparib in platinum-resistant BRCA mutation OCHOXA9 meth-ctDNA is measured using a digital droplet polymerase chain reaction before the baseline and each treatment cycleMethylation status and changes in methylation compared to baselines are associated with total lifetime (OS) and progression-free lifetime (PFS)detected HOXA9 methylctDNA during treatment with PARP inhibitors associated with poorer clinical outcomesThis association is evident after the first treatment cycle and is maintained throughout the treatmentAfter three treatment cycles, the median PFS was 5.1 months in patients without HOXA9 meth-ctDNA, the median PFS was 8.3 months and the median OS was 9.5 months, while the median OS was 19.4 months (P 0.0001 and P.00000, respectively)HOXA9 meth-ctDNA was detected at baseline, but patients who were subsequently undetectable had the most favorable clinical results, followed by those who did not detect the level throughout the processThese associations are maintained in multivariate analysisin summary, the results show that longitudinal monitoring of HOXA9 meth-ctDNA is clinically feasible and closely related to clinical outcomes (PFS, OS), suggesting that it can serve as a valuable predictive biomarker for clinical decision-making for the treatment of platinum drug-resistant BRCAOC mutations by PARP inhibitors