Project: ONco SEnsitive Treatment - Highly sensitive detection of mutations appearing in colon cancer that influence treatment

Background_x000D_Colorectal cancer (CRC) is one of the most common causes of cancer-related deaths and approximately one million new cases are diagnosed each year. Therapeutics targeting the epidermal growth factor receptor (EGFR) is effective for treatment of some of the CRC patients, however 80-90% of the patients do not respond to this rather expensive treatment. Mutations in the oncogene KRAS are correlated with the lack of response to the anti-EGFR drugs and as a consequence an analysis for KRAS mutations is now required before administration of these drugs. Current KRAS testing identifies 30-50% of the non-responders, strongly depending on the sensitivity of the applied assay. Several studies have found that mutations in other genes (BRAF and PIK3CA) lead to anti-EGFR resistance as well, and that an approach combining the use of assays with extremely high sensitivity and the inclusion of more biomarkers will lead to the identification of up to 70% of the non-responders. Besides saving side-effects and wasted time on hopeless treatment for the patients, identification of more of the non-responders can save up to $30.000 per patient in medication expenses. No commercial product on the market today satisfies these demands for very high sensitivity and multiplicity of markers in a ready-to-use kit._x000D__x000D_Aim_x000D_We will develop a kit with unprecedented sensitivity, which will help identifying a higher percentage of the non-responders. The kit will employ several biomarkers relevant to CRC in the same ready-to-use platform. The kit will be competitive in hands-on time and price, and will be utilizing equipment already established in most diagnostic laboratories. Our technological platform is generic and more biomarkers can easily be included as soon as they are discovered in the future._x000D__x000D_Approach_x000D_Our approach is to combine several molecular technologies with a novel, innovative chemistry developed by PentaBase, the SME participant in the consortium. PentaBase has developed a patented technology for chemical modification of oligonucleotides resulting in significant improvement of assays based on real time polymerase chain reaction (RT-PCR), regarding both sensitivity and specificity. This approach has resulted in very promising data in our preliminary studies on KRAS mutation detection. The performance of the assays will in the proposed project be validated by analyzing 100 CRC biopsies and comparing the results to the methods already established at the Institute of Pathology of the Canton Tessin in Switzerland._x000D__x000D_Product_x000D_The project will result in a kit prototype ready for clinical research, approval and market introduction. We expect to develop a kit which is able to identify significantly more of the patients not responding to the anti-EGFR treatment. Moreover, the kit will comprise a proof-of-concept for the generic technology platform, based on PentaBase’s proprietary chemistry. This platform is expected to lead to a whole series of related kits in the future, generating improved diagnostics for the patients, less wasted medication expenses, and more jobs and improved market potential for PentaBase’s technology. The end product will be backed by standard operation procedures and software._x000D__x000D_Market_x000D_The market for KRAS tests is already well established. It is estimated that 300,000 KRAS mutation analyses are performed worldwide each year accounting for more than 37 mio. euro. The market for companion diagnostics is expected to grow as more personalized, targeting therapeutics are developed. There is growing evidence that the biomarkers included in our kit are relevant for a range of other cancer diseases. This means that the number of indications for which the assays will be required will probably increase considerably in the future as new correlations are validated in clinical studies._x000D__x000D_Consortium_x000D_The project benefits from a strong consortium bringing together unique expertise and experiences from each of the Ps. The project Ps include a company with oligonucleotide chemistry expertise and IP in an innovative technological platform, a research organization with strong expertise in assay development and molecular biology, and a research-active pathological medical institution with strong knowledge in KRAS-typing and cancer biopsy handling. The clinical P is of key importance as it represents the future costumer of the end product and as such will be able to give highly qualified feedback on kit performance, protocol outline, and user-friendliness ensuring the best possible settings for a successful introduction of a new and improved kit to the market._x000D_

Acronym	ONSET Diagnostics (Reference Number: 7034)
Duration	15/03/2012 - 15/09/2014
Project Topic	A kit will be developed with unprecedented sensitivity to choose the most efficient treatment of colon cancer, to save pain and money by efficiently identifying non responders. The kit will comprise a proprietary chemistry, well-known molecular strategies and be validated by a benchmark study
Project Results (after finalisation)	As aimed for, we have developed a kit for stratification of colon cancer patients based on KRAS exon 2 mutations. The kit has been tested on clinical samples in a comparison study, head-to-head against the most widely used existing methods. These tests have demonstrated that our kit detects KRAS exon 2 mutations with an unprecedented sensitivity. High sensitivity is of utmost importance in selecting colon cancer patients eligible for efficient treatment with new targeting drugs. The kit is now CE IVD marked and ready for commercialization by the SME P (CO) in the project.
Network	Eurostars
Call	Eurostars Cut-Off 7

Project partner

Number	Name	Role	Country
3	Danish Technological Institute	Partner	Denmark
3	Istituto Cantonale di Patologia	Partner	Switzerland
3	PentaBase ApS	Coordinator	Denmark