Figure 6. AXL expression corresponds to expression of DNA repair proteins and EMT markers in patient cohorts.
A-C) Correlation analysis of AXL protein with other protein markers in NSCLC PROSPECT cohort (A), the TCGA LUSC cohort (B) and the TCGA HNSCC cohorts (C). Heat maps show the top significant markers that correlate with AXL expression (FDR<5%, Spearman Rho value > +/− 0.35). D) Correlation analysis of AXL gene expression with other genes in the breast cancer patient cohort, with heat map showing the top significant markers that correlate with AXL expression. E) Model depicting how AXL inhibition causes HR deficiency and synthetic lethality with PARP inhibitor. In mesenchymal cell lines and tissues, AXL expression leads to higher expression of HR DNA repair proteins, facilitating higher HR-DNA repair efficiency, which is inhibited in the presence of an AXL inhibitor (TP0903). This makes the cells sensitive to inhibition of an alternate DNA repair pathway that utilizes PARP (base excision repair). Thus, a synergy occurs when AXL and PARP are inhibited simultaneously, leading to accumulation of DNA damage and apoptotic cell death.