Molecular Similarities Between Tumors
Protein kinase activity profiling for diagnosis and personalized treatment of cancer
Protein kinases (PKs) affect the catalytic activity, localization and stability of proteins through phosphorylation of these proteins. Abnormal activity of PKs is a cause or consequence of many diseases, especially cancer. The intention to regulate the aberrant kinase activity has made PKs the most important class of protein targets for development of cancer drugs. On the other hand, changes in the PK activity pattern in tissues would signal about the emerging cancer. The information about chances in PK activities could be used for the distinguishing of types of cancer for accelerating (breast) cancer diagnosis and improving the efficiency of treatment of the disease. KINASERA Ltd. has developed fluorescent probes (ARC-Fluo, patents pending) that possess sub-nanomolar binding affinities (comparable to or better than that of good antibodies) towards many PKs of the AGC group (probes for other PKs are currently under development). Differently from most of antibodies ARC-Fluo probes only bind the active form of a PK. Thus the probes can be used for profiling of activity of PKs (concentration of active PKs) in crude tissue samples. High binding affinity affords the application of an ARC-Fluo probe as a detection reagent in combination with specific PK catcher antibodies in bead- or multi-well-based multiplexing high throughput technologies. Mapping of the activity of PKs enables the distinction of types of cancer (e.g., “triple negative” breast cancer) based on different activation of PK-related signaling pathways responsible for the development and progression of cancer. The cost-effective assay technology suitable for massive screening of potential patients is adaptable to instrumental setups of widely used multiplexing assay platforms.
Nov 20, 2011