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