Pediatric sarcoma — STAT3 inhibitor LY5

MERTK in endothelial cells maintains barrier function and restrains neutrophil transendothelial migration, so deleting it specifically in endothelium should aggravate inflammatory lung injury.

Knocking MERTK down in primary human pulmonary microvascular endothelial cells increased neutrophil transmigration and dextran leak and disrupted adherens junctions and basal Rac1 activity, and global Mertk-null mice recruited more neutrophils and leaked more Evans blue during Pseudomonas aeruginosa pneumonia. But inducible endothelium-specific Mertk-null mice showed no difference from controls in either neutrophil migration into inflamed lungs or vascular permeability.

Why it matched: mechanism: Kinase signalling · failed the same way: Held in the model species, not beyond it

A mouse model of breast cancer driven by polyoma middle T antigen would reproduce the systemic changes in monocytes seen in human breast cancer, making it a usable model for studying them.

Tumour-bearing mice did show more monocytes in bone marrow, blood and spleen, from faster proliferation, and transcriptional changes in classical monocytes led by down-regulated type I interferon signalling and antigen presentation. But these transcriptome changes did not match those found in patients with breast cancer.

Why it matched: mechanism: Cell cycle & proliferation · failed the same way: Held in the model species, not beyond it