Fig. 4
Combination treatment of defactinib with paclitaxel shows synergistic lethality in vitro and in vivo. a. Combination index was calculated after treatment of cells (Suit-2, PDAC-1, PDAC-3) with IC25 or IC50 of defactinib in combination with a range of paclitaxel dosing. Combination treatment showed strong synergistic effects in PDAC-1 and synergistic/additive effect in two other cell lines. b. Example of drug curves of primary cell line PDAC-1of defactinib in combination with paclitaxel. c. LC-MS measurement (n = 2) of drug concentration of cells (PDAC-1) exposed to defactinib/paclitaxel/combination showed highest intracellular concentrations of defactinib with combination. d. Polymerized tubulins were significantly highest in PDAC-1 cells treated with combination exposure to monotreatment. e. Growth of tumor size (defined as BLI in pancreas region) was significantly inhibited from day 23 to 31 in the nab-paclitaxel and combination group (multiple t-test, corrected for multiple testing by Holm-Sidak test)