Tumor response to NAC predicts survival and can be considered a surrogate prognostic marker. Three tiered chemotherapy response score (CRS) of omental tissue sections showed a significant association with survival. In patients with CRS 1 or 2, NAC selects a subpopulation of chemotherapy resistant tumor cells. Residual tumors remaining after neoadjuvant chemotherapy contain cell population intrinsically resistant to chemotherapy. However, the standard of care for patients who have residual disease after NAC is the same regimen, as therapies that would be effective in reducing recurrences are unknown. We hypothesize that comprehensive molecular analyses of residual disease after NAC measured by targeted sequencing and Immunohistochemistry would be helpful to find out innovate new therapeutic targets.
During the study period between 2006 and 2017, Pre- and post NAC tumor tissue samples were collected from patients with advanced HGSC. Combined NGS and IHC was performed to identify actionable target and pathway activation in chemo-resistant tumor cells. We examined whether profiling residual HGSC after NAC identifies targetable molecular lesions in the chemotherapy-resistant component of tumor.
Alteration in TP53 were identified in 76 of 104 post-NAC samples (72.1%). HRR gene alteration were found in 30 of 104 post-NAC samples (28.8%). Patients with DNA repair alterations (BRCA1, BRCA2, ATM mutations) were found in 30% of HGSC and they had better chemotherapy sensitivity and survival outcomes than those with intact DNA repair system. Otherwise, rare individual actionable targets (less than 5%) were found in most of patients.
We showed the genomic landscape of drug-resistant tumor cells remaining in advanced HGSC after NAC.
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All authors have declared no conflicts of interest.