Kinome Profiling Tool for Personalized Cancer Medicine

In this project, we will develop a Kinome Profiling Tool that will provide medical experts with a detailed view of irregular protein kinase activity in a cancer patient sample. The tool will enable to select the kinases inhibitors that are effective for an individual cancer case. The suggested Kinome Profiling Tool will entail unique imaging technology, application protocols and an advanced analysis software. The project will address technical aspects of kinome profiling, as well as testing patient materials collected through biopsy and resection from cancer patients. The Kinome Profiling Tool will primarily target research units at hospitals providing cancer treatment and cancer care units as it is expected that the majority of them are involved in patient screening and tumor profiling in order to prescribe the best possible and most cost efficient treatments. The list of breast cancer related kinases and their mapping schema to key signaling pathways has been finalized. The selectin of kinases and pathway mappings are based on the expertise of our academic partner and other commercial tools that focuses on kinases in cancer. The selection substrate clusters have been chosen in order to have the least amount of cross-talk between the different kinases. Each substrate cluster consists of the 4 most unique substrates to represent each kinase. These arrays are have been tested using pure kinases and two different cell lysates.. This is done in collaborating with the Radium Hospital, using both pure kinases and cell-lyzates. The results show very good reproducibility across the various duplicates on the slide we see clear differences in the phosphorylation patterns of the different lysates. Thus allowing us to deduce specific kinase profiles for the different cell lysates and identify tissue specific kinases in the different breast cancer sub groups. We are currently evaluating our IP strategy for the unique arrays, and are in dialogue with Dehns on how to best protect the array design. We are confident that the current application protocols are close to optimal, but we believe that as more and more experiments are being set up that our user experience will allow for even further optimization. These new protocols have been successfully used in lysate experiments both for smaller test arrays (200 substrates from mixed organisms), full arrays (1000 substrates from human) and our custom designed arrays, and show good signal to noise ratio. The raw data analysis software has now includes advanced presentation features like heat maps, XY-plots and bar charts for better overview and improved understanding of the data. These new features are seamlessly integrated with image export, pathway analysis pipeline/software. Several grid templates, covering different array designs have been included supporting easy comparison of different experiments (eg. Treated vs untreated samples). Improvements have been made with respect to the kinase profile analysis, clustering and mapping to stat of the art literature. The kinase profiling module currently include: 1) clustering functionality allowing the user to analyses selections of kinases based on common properties e.g. increased or decreased activity, commonly associated disease etc. 2) drugs mapping, providing the user with known drugs associated to the different kinases, 3) Clinical trial mapping, providing an overview of clinical trial involving kinase related biomarkers or inhibitors, 4) pathway mapping, allowing data analyzis in the context of pathways. We will continue to extend the analysis software for combing kinase profiles with mutation analysis based on NGS data.

The primary objective is a Kinome Profiling Tool that will provide medical experts with a detailed view of irregular protein kinase activity in a cancer patient sample. The tool will enable to select the kinases inhibitors that are effective for an indivi dual cancer case. The motivation is the understanding that kinases have a known association with cancer, and that these can be examined in parallel. The suggested Kinome Profiling Tool will entail a unique imaging technology based on a double sided silico n detector (DSSD), and provide advanced analysis software and protocols. The research will address technical aspects of kinome profiling, as well as testing patient materials collected through biopsy and resection from cancer patients. We shall solve iss ues of reproducibility in measured results, survey the problems of kinase-substrate cross reactivity, optimize target substrate presentation on the microarray slide, optimize the selectivity of substrates for our model disease, explore different ways of h ow to map these substrates to known cancer pathways, and analysis of the kinome profiling by mapping and prediction algorithms. Biomolex will offer the Kinome Profiling Tool to diagnostics and research labs, kinome profiling service providers, and pharma ceutical enterprises. There are over 1,400 cancer treatment units only in the US accredited by the American College of Surgeons. Based on the US market, we can assume that there are approximately 3 000 cancer care/treatment units in the western world. Th ese units collectively treat over 70% of all newly diagnosed cancer patients, and have at least one or more accredited tumor boards. Tumor boards are typically composed of medical, surgical and radiation oncologists. The Kinome Profiling Tool will primari ly target these units as it is expected that the majority of them are involved in patient screening and tumor profiling in order to prescribe the best possible and most cost efficient treatments.