Figure 4. Targeting AXL1 expressing TNBC with combination of cabozantinib and IACS-10759.
(A-B) Two AXL1 high TNBC PDXs (BCX.010; A and BCX.084, B) were treated with cabozantinib (20 mg/kg, po, daily) and IACS-10759 (5 mg/kg, po, 5 days on 2 days off) prolonged tumor stability compared to either single agent alone. (C) A low AXL1 expressing PDX that is relatively more sensitive to IACS-10759 was treated with cabozantinib (20 mg/kg or 5 mg/kg, po, daily) and IACS-10759 (5 mg/kg, po, 5 days on 2 days off) and both combinations resulted in tumor regression from baseline. Data shown mean +/−SEM. **=p<0.001. (D) In the PI3KCA mutant PDX (BCX.010), the combination of cabozantinib and IACS-10759 significantly inhibited PI3K/mTOR pathway to a greater extent that either single agent along as evidenced by decrease phosphorylation of ribosomal protein S6 on RPPA. *=p<0.05; **=p<0.01