Khayal Gasimli

Best original research presented at the 26th European Congress on Gynaecological Oncology: Best of ESGO 2025

Sequential Targeting of PLK1 and PARP1 Reverses the Resistance to PARP Inhibitors and Enhances Platin-Based Chemotherapy in BRCA-Deficient High-Grade Serous Ovarian Cancer with KRAS Amplification

Ovarian cancer (OC) accounts for approximately 4% of cancer deaths in women worldwide and is the deadliest gynecologic malignancy. High-grade serous ovarian cancer (HGSOC) is the most predominant ovarian cancer, in which BRCA1/2 gene mutation ranges from 3 to 27%. PARP inhibitors (PARPi) have shown promising results as a synthetically lethal therapeutic approach for BRCA mutant and recurrent OC in clinical use. However, emerging data indicate that BRCA-deficient cancers may be resistant to PARPi, and the mechanisms of this resistance remain elusive. We found that amplification of KRAS likely underlies PARPi resistance in BRCA2-deficient HGSOC. Our data suggest that PLK1 inhibition restores sensitivity to PARPi in HGSOC with KRAS amplification. The sequential combination of PLK1 inhibitor (PLK1i) and PARPi drastically reduces HGSOC cell survival and increases apoptosis. Furthermore, we were able to show that a sequential combination of PLK1i and PARPi enhanced the cellular apoptotic response to carboplatin-based chemotherapy in KRAS-amplified resistant HGSOC cells and 3D spheroids derived from recurrent ovarian cancer patients. Our results shed new light on the critical role of PLK1 in reversing PARPi resistance in KRAS-amplified HGSOC, and offer a new therapeutic strategy for this class of ovarian cancer patients where only limited options currently exist.

Association between resection margin and local recurrence in the treatment of primary squamous cell vulvar carcinoma

Our aim was to assess the potential correlation between resection-free margin and local recurrence in the treatment of squamous cell vulvar carcinoma (SCC). Seventy-five patients with primary SCC of the vulva and adequately follow-up that were operated in our university hospital between January 2008 to December 2018, were retrospectively evaluated with focus on resection-free margin and its impact on local recurrence. Several prognostic factors were analysed for possible correlation. Median patient age and follow-up was 62.8 years and 57.4 months, respectively. Among all patients, 27 (36%) local recurrences were documented, for a median local recurrence-free survival (LRFS) of 68.1 months for patients resected R0 and 65.6 months for those initially R1 resected (p=0.750). There was also no statistically significant difference (p=0.750) when evaluating the LRFS relative to the absence or not of inguinal lymph node involvement, although there was a numerical difference of approximately 17 months (73.9 vs. 57.3 months). For initially R0 resected patients, no significant influence of the resection-free margin in millimeters on LRFS was noted for a median of 58.4 versus 57.3 months for patients with a free margin of 0.1-3 mm and those with a free margin of >3 mm, respectively (p=0.800). Eleven patients received adjuvant chemoradiotherapy, all for nodal inguinal involvement. Among them, 5 patients developed recurrence, while the other 6 remained free of disease. The extend of resection-free margin does not appear to adversely affect LRFS suggesting that smaller margins could be applied to minimize morbidity without compromising local control.