Protein kinases are a family of about 535 enzymes that, collectively, are termed the Kinome. Uncontrolled protein kinase activity has been linked to the development of nearly 25% of all cancers and, as a result, many kinase-specific inhibitors are currently approved for therapy of various cancer types. However, most of these kinase inhibitors target a relatively small fraction of the human Kinome and approximately 50% of it remains largely uncharacterized with respect to the role of these kinases in cancer. Several CRISPR/cas9 and/or RNAi loss-of-function studies have shown that many uncharacterized kinases are essential for cancer cell viability highlighting the therapeutic potential of the “dark” kinome. Additionally, the activation of the alternate “dark” kinase can cause bypassing the action of a highly specific kinase inhibitor resulting in drug resistance. Therefore, “dark” protein kinases represent one of the most promising avenues for cancer therapy.
Summary of the Invention
Dr. James Duncan at Fox Chase Cancer Center has developed and tested the assay to discover the “dark” kinome profile of cancer cell for prognostic criteria of disease and therapeutic potential of selected kinase inhibitors. Multi-analyte columns containing several layers of multiplexer inhibitor beads, wherein each layer has specific immobilized kinase inhibitors with binding affinity for multiple kinases, can be used to generate a kinome profile of a single cell or the patient. The presence of the measured level or phosphorylation status of at least one kinase that is comparable to the cancer standard level indicates that the subject has cancer or is at risk of developing it. Accordingly, the analysis of the kinome profile of the patient and comparison it to a standard cancer kinome profile can confirm the diagnosis, determine a cancer treatment regimen, assess a treatment regimen based on the monitoring analysis of kinase activity, improve the effectiveness of ongoing therapy, and predict the development of drug resistance.
Thereby, the ability to select a personalized course of therapy or treatment regimen, i.e., to be able to choose a less aggressive treatment or to alter treatment from aggressive to less aggressive at a time prior to the conventional end of a treatment regimen can provide less anguish and suffering for the patient on both an emotional and physical level.
Patent Status: A patent application has been filed.
For Licensing/Partnering information, please contact:
Inna Khartchenko, MS, MBA
Director, Technology Transfer and New Ventures