Debio 0617B inhibits growth of STAT3-driven solid tumors through combined inhibition of JAK, SRC, and class III/V receptor tyrosine kinases

摘要: Tumor survival, metastases, chemoresistance, and escape from immune responses have been associated with inappropriate activation of STAT3 and/or STAT5 in various cancers, including solid tumors. Debio 0617B has developed as a first-in-class kinase inhibitor unique profile targeting phospho-STAT3 (pSTAT3) pSTAT5 tumors through combined inhibition JAK, SRC, ABL, class III/V receptor tyrosine kinases (RTK). showed dose-dependent pSTAT3 STAT3-activated carcinoma cell lines; also potent antiproliferative activity panel cancer lines patient-derived tumor xenografts tested an vitro clonogenic assay. vivo efficacy by inhibiting growth several mouse xenograft models. To increase inhibition, was combination the EGFR erlotinib non-small lung model. evaluate impact blockade on orthotopic Measurement primary weight metastatic counts tissue demonstrated therapeutic this These data show broad spectrum STAT3-driven synergistic inhibition. Mol Cancer Ther; 15(10); 2334-43. ©2016 AACR.