Fig. 6.

Combinatorial treatment with TrkA- and EphA2- targeting inhibitor delays tumor growth and survival and block the brain metastasis. A After tumor relapse from MDA-MB-231 HA-TrkA were xenografted in SCID mice treated with Entrectinib and/or EphA2-targeting siRNA 5 times every 2–3 days. B Cleared brain from control xenografted mice was sliced and labeled for laminin (blood vessel, red) and human HLA (MDA-MB-231-TrkA, white). C 3D projection of solvent-cleared brain (blue, autofluorescence) dissected from xenografted SCID mice with MDA-MB-231-TrkA revealed by human HLA immunostaining (white). D Detection of metastatic MDA-MB-231-TrkA (by RT-PCR for the human microglobulin expression) in brain, liver and lung from xenografted SCID mice treated with Entrectinib and/or siEphA2. E Survival of mice xenografted with survival median (red dotted line). All data are derived from the same experimental approach detailed in A. For E, the experiment was performed with 7 mice/group. At the end of this experiment, 1 mouse/group was used for B and C, and 6 mice/group were used for D. Data in E are represented by a staircase graph with median (red dotted line). For E, Mantel-Cox Log-rank analysis was realized, P-value shows the comparison between CTRL and combinatorial treatment. For B, scale bar = 1 mm, and scale bar = 30 µm for C