Fig. 2

Targeting FAK synergizes with doxorubicin/PLD in the treatment of cancer in both preclinical and clinical settings. A Cell viability assay for doxorubicin across 5 different ovarian cancer cell lines. Cells were treated with serially diluted doxorubicin beginning with 20 μM for 72 h. The factor for each subsequent dilution is 4. (n = 3 per point). B-F Cell viability evaluation for the combination of IN10018 and doxorubicin across 5 different ovarian cancer cell lines. Each cell line was treated with 5 μM IN10018 in combination with 0.125x, 0.25x, 0.5x, 1x, 2x, or 4 × IC50 of doxorubicin. The treatment lasted 72 h. From the cell viability assay from (A-F), the CCK8 reagent was used for cell viability evaluation. (n = 3 per point). G-H Evaluation of the combined effects of IN10018 and PLD in 2 human ovarian cancer models, TOV21G and LD1-0032–361282 (n ≥ 3 per group). I-J The drug combination effects of IN10018 and PLD in 1 human head and neck cancer PDX model HN-13–0286 and 1 human small cell lung cancer PDX model LU5164 (n ≥ 4 per group). For animal studies from (G-J), IN10018 was dosed orally at 12.5 mg/kg or 25 mg/kg once daily. PLD was dosed at 1.5 mg/kg or 3 mg/kg by tail vein injection once weekly. K The swimmer plot graph for the 10 patients who showed latency responses to the combination regimen with IN10018 and PLD. The duration of responses of patients with SD, PR, and PD was assessed according to RECIST 1.1. L The variation of tumor sizes across the 10 patients at the first imaging and at the time showed the largest tumor loss. M The tumor variation of the target lesion of patient No.8 throughout the different phases of treatment with IN10018 in combination with PLD. Data represent mean ± SEM. Statistical analysis was done using the unpaired student's T-test. *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001