E!11086 KINOME PROFILING TOOL FOR PERSONALIZED CANCER MEDICINE

Optimization and calibration of the Biomolex instruments and software have been finalized. The array design is finalized, and multiple experiments have been done using the designed array. We also developed and optimized the various application protocols with respect to stability and robustness. As a research tool they work satisfactory, however, we feel that further improvements are necessary for a clinical application. These improvements will be done in collaboration with OUS after this project. We have run several kinase and cell-line experiments using both isotope protocols and fluorescent protocols. The results from the MDAMB 231 (isotope protocols) gave very good images with good reproducibility (internally on one slide and across different slides). For some of the other breast cancer cell-lines MCF7 and KPL4 the quality of the images was variable suggesting the need for further experiments in order to draw any firm conclusions. On the positive side, we observe different phosphorylation patterns for the cell-lines. The inhibitor studies did not progress as anticipated, multiple analysis was set up without yielding anticipated results. We will continue this work together with Oslo University Hospital after this project. We have developed a pathway analysis module for analyzing and linking the results to pathway-related information. We have also developed tools for visualizing our kinome profiles in combination with other omics data. During our discussions with key opinion leaders, we have presented the results and the experienced challenges. So far, the conclusion is that the kinase profiling regardless of the inhibitor is definitely of interest and can guide researchers in identifying potentially targetable kinases. Successful setup with inhibitor studies will increase the value of the pipeline since it will then be possible to test and verify specific inhibitors and combinations thereof. We have run several kinase and cell-line experiments using both isotope protocols and fluorescent protocols. The results from the MDAMB 231 (isotope protocols) gave very good images with good reproducibility (internally on one slide and across different slides). For some of the other breast cancer cell-lines MCF7 and KPL4 the quality of the images was variable suggesting the need for further experiments in order to draw any firm conclusions. On the positive side, we observe different phosphorylation patterns for the cell-lines. The inhibitor studies did not progress as anticipated, multiple analysis was set up without yielding any concrete results. We will continue this work together with Oslo University Hospital after this project. We have developed a pathway analysis module for analyzing and linking the results to pathway-related information. We have also developed tools for visualizing our kinome profiles in combination with other omics data. During our discussions with key opinion leaders, we have presented the results and the experienced challenges. So far, the conclusion is that the kinase profiling regardless of the inhibitor is definitely of interest and can guide researchers in identifying potentially targetable kinases. Successful setup with inhibitor studies will increase the value of the pipeline since it will then be possible to test and verify specific inhibitors and combinations thereof.

This project will enable Biomolex to meet several milestones towards the successful realization of the Kinome Profiling Tool. The results collected in the project will position Biomolex to raise more capital from major investors, seed capital or additional development grants to further its development plans beyond the current project. The developments in this project can be included in future cancer medicine, where kinome profiling will be an important part in determining optimal treatment.This project is expected to allow us to enter into the hospital and cancer treatment facilities sector and the the collaboration with Pepscope will provide Biomolex a strong foothold within the international service provider market. It is also expected that that our core technology and our analysis software will greatly benefit from the algorithms and technological advancements from this project.

The underlying idea is to improve precision cancer medicine by developing a new tool (Kinome Profiling Tool) and service pipeline to measure kinase activity from clinical samples. The tool and accompanying methods will produce "kinome profiles" to be used by physicians to exploit the connection between kinases and cancer, and help assess treatment and prognosis for individual cancer patients. Kinase inhibitors are the largest class of new cancer drugs. There are currently 22 small molecule kinase inhibitors approved as anti-cancer drugs. Interest has been fueled by the realization that kinases are intimately involved in cancer cell growth, proliferation and survival. Indeed, kinases and their direct regulators are among the most frequently mutated oncogenes and tumor suppressors. Several cancer treatments are designed to inhibit aberrantly activated kinases to prevent cell division. In this project we aim to exploit the new direction that is ongoing in cancer research, namely the development of personalized and more precise cancer medicine. We will develop kinome profiling tools, software and design profiling arrays. These elements will be used to develop complete pipeline for offering kinomoe profiling services.