DDR1 Inhibition Enhances Immunotoxin Therapy

Recombinant immunotoxins (RIT) have been highly successful in cancer therapy due, in part, to the high cancer-specific expression of cell surface antigens such as mesothelin, which is overexpressed in mesothelioma, ovarian, lung, breast, and pancreatic cancers, but is limited in normal cells. RG7787 is a clinically optimized RIT consisting of a humanized anti-mesothelin Fab fused to domain III of Pseudomonas exotoxin A, in which immunogenic B-cell epitopes are silenced. To enhance the therapeutic efficacy of RITs, we conducted a kinome RNAi sensitization screen, which identified discoidin domain receptor 1 (DDR1), a collagen-activated tyrosine kinase, as a potential target. The collagen/DDR1 axis is implicated in tumor–stromal interactions and potentially affects tumor response to therap...

from MedWorm: Mesothelioma http://medworm.com/index.php?rid=170203238&cid=c_409_6_f&fid=33679&url=http%3A%2F%2Fcancerres.aacrjournals.org%2Fcontent%2F76%2F6%2F1560.short%3Frss%3D1