RON - The Con in Colorectal Carcinoma

Abstract

Abstract:The recepteur d'origine nantais (RON) is a member of MET family of receptor tyrosine kinase (RTKs), an overexpression of which has been observed in several cancers. The expression of RON gene is required during embryonic development and also plays critical roles in regulating macrophage inflammatory response. In CRC, the overexpression of moderate RON activity contributes to their oncogenic potential by regulating several key processes such as proliferation, motility and resistance to apoptosis. Interestingly, an aberrant RON expression is often associated with the generation of several splice variants with unique transforming activities. The targeting of RON signaling pathway by the use of monoclonal antibodies and small-molecule inhibitors has shown promising therapeutic results in animal models. The present article aims at summarizing the current understanding of RON kinase in CRC.

Design, synthesis and RON receptor tyrosine kinase inhibitory activity of new head groups analogs of LCRF-0004

“…Activation of RON RTK by MSP triggers downstream signaling pathways (b-catenin, PI3K/Akt, MAPK, NF-jB and STAT3) which mediate a number of biological events including macrophage activity and tissue repair, and epithelial cell behavior (cell growth, motility, and epithelial to mesenchymal transition). Aberrant activity of RON has been described in numerous types of cancers including colorectal, 2 breast, 3 lung, 4 pancreas 5 and prostate 6 and occurs mainly through wild type receptor overexpression or expression of isoform variants harboring different truncations within the extracellular domain, leading to enhanced and uncontrolled tyrosine kinase activity suggesting their potential interest as promising therapeutic targets for cancer therapy. Importantly, overexpression of RON in tumor tissues correlates with increased metastasis and poor prognosis in human cancer patients.…”