Inhibition of SYK kinase does not confer a pro-proliferative or pro-invasive phenotype in breast epithelium or breast cancer cells.

SYK has been reported to possess both tumour promotor and repressor activities and deletion has been linked to a pro-proliferative / pro-invasive phenotype in breast tumours. It is unclear whether this is a consequence of protein deletion or loss of kinase activity. The SYK inhibitor, BI 1002494, caused no increase in proliferation in breast cancer cells or primary mammary epithelial cells in 2D or 3D cultures, nor changes in proliferation (CD1/2, CDK4, PCNA, Ki67) or invadopodia markers (MMP14, PARP, phospho-vimentin Ser56).

First-in-class ruthenium anticancer drug (KP1339/IT-139) induces an immunogenic cell death signature in colorectal spheroids in vitro.

The ruthenium complex sodium trans-[tetrachloridobis(1H-indazole)ruthenate(iii)] (KP1339/IT-139) showed preclinical activity in a variety of in vivo tumor models including a highly predictive colon cancer model. The compound has entered clinical trials, where patients experienced disease stabilization accompanied by mild side effects. KP1339, a GRP78 inhibitor, disrupts endoplasmic reticulum (ER) homeostasis leading to cell death.