| Title: | In vitro evaluation of electrochemotherapy combined with sotorasib in pancreatic carcinoma cell lines harboring distinct kras mutations |
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| Authors: | ID Jesenko, Tanja (Author)
ID Omerzel, Maša (Author)
ID Živič, Tina (Author)
ID Serša, Gregor (Author)
ID Čemažar, Maja (Author) |
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| Files: |  URL - Source URL, visit https://pmc.ncbi.nlm.nih.gov/articles/PMC12346384/
 PDF - Presentation file, download (743,73 KB)
MD5: 30499687CEC5BE528FAC17BAADEE9044
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| Language: | English |
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| Typology: | 1.01 - Original Scientific Article |
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| Organization: |  OI - Institute of Oncology
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| Abstract: | 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. |
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| Keywords: | bleomycin, cisplatin, electrochemotherapy, pancreatic cancer |
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| Publication status: | Published |
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| Publication version: | Version of Record |
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| Submitted for review: | 30.05.2025 |
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| Article acceptance date: | 22.07.2025 |
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| Publication date: | 24.07.2025 |
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| Place of publishing: | Basel |
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| Publisher: | MDPI, Basel, Switzerland |
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| Year of publishing: | 2025 |
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| Number of pages: | str. 7165-1-7165-10 |
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| Numbering: | Vol. 26, no. 15 |
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| Source: | Basel, Switzerland |
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| PID: | 20.500.12556/DiRROS-24008  |
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| UDC: | 602 |
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| ISSN on article: | 1422-0067 |
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| DOI: | 10.3390/ijms26157165 |
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| COBISS.SI-ID: | 245948931 |
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| Note: | Nasl. z nasl. zaslona;
Opis vira z dne 19. 8. 2025;
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| Publication date in DiRROS: | 26.11.2025 |
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| Views: | 95 |
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| Downloads: | 47 |
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