Pancreatic cancer is a severe malignancy with increasing incidence and high mortality due to late diagnosis and low sensitivity to treatments. Search for the most appropriate drugs and therapeutic regimens is the most promising way to improve the treatment outcomes of the patients. This study aimed to compare (1) in vitro efficacy and (2) in vivo antitumor effects of conventional paclitaxel and the newly synthesized second (SB-T-1216) and third (SB-T-121605 and SB-T-121606) generation taxanes in KRAS wild type BxPC-3 and more aggressive KRAS G12V mutated Paca-44 pancreatic cancer cell line models. In vitro, paclitaxel efficacy was 27.6 ± 1.7 nM, while SB-Ts showed 1.7-7.4 times higher efficacy. Incorporation of SB-T-121605 and SB-T-121606 into in vivo therapeutic regimens containing paclitaxel was effective in suppressing tumor growth in Paca-44 tumor-bearing mice at small doses (≤3 mg/kg). SB-T-121605 and SB-T-121606 in combination with paclitaxel are promising candidates for the next phase of preclinical testing.

3rd Faculty of Medicine Charles University 100 00 Prague Czech Republic

Department of Biochemistry Cell and Molecular Biology 3rd Faculty of Medicine Charles University 100 00 Prague Czech Republic

Department of Pathology University Hospital Kralovske Vinohrady 100 00 Prague Czech Republic

Department of Surgery University Hospital Kralovske Vinohrady 100 00 Prague Czech Republic

Institute of Biotechnology of the Czech Academy of Sciences BIOCEV Research Center 252 50 Vestec Czech Republic

Institute of Chemical Biology and Drug Discovery State University of New York at Stony Brook Stony Brook NY 11794 3400 USA

Laboratory of Pharmacogenomics Biomedical Center Faculty of Medicine in Pilsen Charles University 323 00 Pilsen Czech Republic

Toxicogenomics Unit National Institute of Public Health 100 00 Prague Czech Republic

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