Introduction Nowdays, PARP inhibitor(PARPi) is frequently used as maintainace treatment in ovarian cancer patients. Due to the DNA repair defect, BRCA1/2 deficient tumor cells are more sensitive to PARP inhibitors (PARPi) through the mechanism of synthetic lethality. When progressed after using the parp inhibitor, the genomic alteration of the tumor and the reuse of the parp inhibitor were not considered.
Methods A slide was producted for patients who started 1st parp inhibitor from February 2018 to May 2022, and for patients with tissues before and after 1st parpinhibitor treatment. We analyzed 20 matched tissue samples before and after progression on first exposure to PARPi among patients undergoing re-treatment with PARPi to understand the genomic changes, potential implication in resistance mechanism and response to PARPi re-treatment.
Results 10 patients were platinum sensitive and 10 patients were platinum resistant.
The histological type was identified as High grade serous carcinoma at 90% and endometrioid carcinoma at 10%.
LOH score increased in 15 patients (88%). TMB increased in 13 patients (76%). The average PARP inhibitor usage period in the platinum sensitive group was 14.65 months which is longer than that of platinum resistant group 6.15 months. Analyzing the period of use, the shorter the first PARP inhibitor, the shorter the period of use of the 2nd PARP inhibitor. The most frequently detected gene was MYC amplification and RAD 21 amplification. (n=2)
Conclusion/Implications Post-specific mutations occur and LOH and TMB increase upon progression with PARP inhibitor. Further research on resistance mechanism in case of recurrence using PARP inhibitor is needed.
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