400 Implementation and feasibility of prophylactic bilateral salpingectomy at Benign, minimally invasive hysterectomy in Styria (Austria)

C Hütter, K Tamussino, K Simon, M Kratky, C Mutz-Eckhart, M Blatt-Gunegger, S Klammer, C Bermann, A Huber, V Lessiak
2021 Ovarian cancer   unpublished
commercially available AKT and DNAPK inhibitors with cisplatin, and elucidate their mechanism of action within the PI3K/ AKT/mTOR pathway. Methodology Platinum resistant immortalised HGSOC cell lines (PEO4, PEA2, OVCAR8, Kuramochi) were treated with cisplatin plus/minus AKT or DNA-PK inhibitors and Isobologram assays performed to establish synergy/antagonism between drug treatments. Cells were treated with inhibitors plus/minus cisplatin at different time points, protein lysates collected, and
more » ... everse Phase Protein Array (RPPA) proteomics performed and analysed to establish mechanisms of action of inhibitors on the PI3K/AKT/mTOR pathway. Result(s)* Following treatment with cisplatin in combination with AKT or DNA-PK inhibitors, different levels of synergy were observed in platinum resistant HGSOC cell lines; strong synergy was noted for AKT inhibitors Afurosertib, Uprosertib, and Triciribine. Proteomic analysis revealed a response signature for AKT or DNAPK inhibition showing activation of AKT at S473 and decrease of downstream targets pS6_235/ 236 and 240/44, and p70S6K_T389. Conclusion* In the platinum resistant immortalised HGSOC cell lines tested, AKT inhibitors showed a synergistic effect when used in combination with cisplatin. Proteomic analysis confirmed targeting of the PI3K/AKT/mTOR pathway. With the aim of resensitising a resistant patient to their platinumbased chemotherapy a synergistic effect between the resensitising compound and chemotherapy agent is essential; this data suggests targeting of the PI3K/AKT/mTOR pathway in platinum-resistant HGSOC patients with AKT or DNAPK inhibition is a potentially useful therapeutic strategy.
doi:10.1136/ijgc-2021-esgo.397 fatcat:vg3a7ugywzcrlc7pxddnbj6jjm