20.500.12556/DiRROS-24008 In vitro evaluation of electrochemotherapy combined with sotorasib in pancreatic carcinoma cell lines harboring distinct kras mutations Pancreatic cancer is among the deadliest malignancies, with limited treatment options and poor prognosis. Novel strategies are therefore urgently needed. Sotorasib, a KRAS G12C-specific inhibitor, offers targeted treatment for a small subset of patients with this mutation. Electrochemotherapy (ECT), which enhances the cytotoxicity of chemotherapeutic agents through electroporation-induced membrane permeabilization, has shown promise in various tumor types, including deep-seated malignancies such as pancreatic cancer. Combining ECT with sotorasib may potentiate antitumor effects in KRAS G12C-mutated pancreatic cancer; however, preclinical data on such combinations are lacking. This proof-of-concept study evaluated the cytotoxic effects of ECT using bleomycin (BLM) or cisplatin (CDDP) in combination with sotorasib in KRAS G12C-mutated MIA PaCa-2 and KRAS G12D-mutated PANC-1 pancreatic cancer cell lines. ECT alone significantly reduced cell viability, particularly in MIA PaCa-2 cells, where electric pulses induced approximately 75% cell death. Combining ECT with sotorasib resulted in an additive effect on KRAS G12C-mutated MIA PaCa-2 cells, though no synergy was observed, likely due to the high intrinsic sensitivity to electric pulses. These results support the potential of combining physical and molecular therapies in a subset of pancreatic cancer patients and lay the groundwork for further in vivo studies to optimize treatment parameters and explore clinical translatability. bleomycin cisplatin electrochemotherapy pancreatic cancer bleomicin cisplatin elektrokemoterapija rak trebušne slinavke true false true MDPI, Basel, Switzerland Basel, Switzerland Angleški jezik Slovenski jezik Neznano 2025-11-06 03:38:35 2025-11-26 10:51:27 2025-11-27 03:58:53 0000-00-00 00:00:00 2025 0 Basel 0 Nasl. z nasl. zaslona; Opis vira z dne 19. 8. 2025; str. 7165-1-7165-10 no. 15 Vol. 26 2025 0000-00-00 Zaloznikova Objavljeno apc 2025-05-30 2025-07-22 2025-07-24 602 1422-0067 10.3390/ijms26157165 245948931 https://pmc.ncbi.nlm.nih.gov/articles/PMC12346384/ 1 b1d67394-bab9-11f0-94a7-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=35657 RAZ_Jesenko_Tanja_2025.pdf RAZ_Jesenko_Tanja_2025.pdf 1 30499687CEC5BE528FAC17BAADEE9044 405c0446ef23d6df2d6caedfa91dff20aeaf0846003f3876f8d24db386fef99f 5c0c497b-caad-11f0-94a7-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=36269 Onkološki inštitut Ljubljana 0 0 0