Project: Sensitive Screening from small samples in treatment of non-small-cell lung cancer
Background_x000D_Non-small-cell lung cancer (NSCLC) is the most widespread type of lung cancer and accounts for the highest mortality rates among cancers. NSCLC is relatively insensitive to chemotherapeutics and radiation therapy, but recently a number of new drugs have been developed. A drawback of these new drugs is that their efficiency is strongly dependent on the genetic make-up of the individual cancer. Therefore it is extremely important to stratify the patients to ensure that they are treated with the optimal medication. In the majority of cases, only small tumor biopsies are available, and it is a major challenge to have enough tumor sample for the genetic tests after the initial NSCLC diagnosis has been made by microscopy. Another drawback of the drugs is that more than 50% of patients treated with targeted therapies will develop resistance to the drugs within 12 months. In 50-60% of the cases this resistance arise from a new mutation at codon 790 in the EGFR-gene, not detectable at treatment start. As soon as this alteration is recognized the treatment should be changed to another drug. Hence, there is also an unmet need for detection of this particular mutation at an earlier stage and preferably from blood samples._x000D__x000D_Aim and product_x000D_We will meet these unmet needs by development of two kits, both based on real time polymerase chain reaction (real time PCR): A diagnostic kit (A) for use on lung biopsies to ensure the best medication is chosen at treatment start, and a monitor kit (B) for use on blood samples to monitor for acquired drug-resistance during treatment. The diagnostic kit (A) will be a highly sensitive kit, employing all the relevant genetic biomarkers and in the same ready-to-use platform saving not only time and costs, but most importantly sample material. The monitor kit (B) will employ the most relevant resistance marker. Both kits will be based on a novel DNA chemistry, have unprecedented sensitivity, will be competitive in hands-on time and price, and will be utilizing equipment already established in most diagnostic laboratories. The project will result in kit prototypes, ready for clinical research, approval and market introduction._x000D__x000D_Approach_x000D_PentaBase, the SME participant in the consortium has developed a proprietary modification of oligonucleotides resulting in significant improvement of assays based on real-time PCR, regarding both sensitivity and specificity. Our approach is to combine several molecular technologies with this novel chemistry using both DNA- and RNA-extracts as templates in the reactions. The individual assays as well as the multiplexed assays will be optimized on plasmids representing each of the genetic alteration. The performance of the diagnostic kit (A) will be validated by analyzing 200 NSCLC biopsies and comparing the results to existing methods. The performance of the monitor kit (B) will be validated on 50 paired blood and tumor biopsy samples._x000D__x000D_Market and effect_x000D_The market for molecular diagnostic tests for NSCLC is well established. With more than 1.6 million new lung cancer patients world wide each year, and molecular diagnostics being more and more important for the treatment of the patients, we estimate that mutation analyses market size is btw 150-450 m€ per year. The market for companion diagnostics is expected to continue to grow as more personalized, targeting therapeutics are developed. Thorough genetic analyses of the tumor and metastases will save the patient for side effects and society for medical expenses on worthless treatments and in the end help extend human lives. The limited amount of available sample is a central challenge in the current diagnostic algorithm and this challenge is expected to be even more profound in the future, as the number of relevant biomarkers and drugs are constantly increasing. No commercial product on the market today satisfies the demands for very high sensitivity and multiplicity of markers in a ready-to-use kit, nor the following of patients._x000D__x000D_Consortium_x000D_The project brings together strong Ps with unique expertises including a company with a proprietary and innovative oligonucleotide chemistry and expertise, a research organization with strong expertise in assay development and molecular biology, and a research-active pathological medical institution with strong knowledge in NSCLC-typing and cancer biopsy handling. Furthermore the consortium will include a pathology laboratory from a hospital in Italy as subcontractor, who will be delivering further clinical samples (paired bioptic and blood samples), clinical evaluation and user feedback regarding the new assays. The clinical Ps are of key importance as they represent the future costumer for the end product and as such will be able to give highly qualified feedback on clinical needs, 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.
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Acronym
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SensiScreen Lung
(Reference Number: 8421)
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Duration
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27/11/2013 - 27/11/2016
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Project Topic
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Using novel DNA chemistry we will develop diagnostic kits tailor-made for Lung Cancer fulfilling the need for extreme sensitivity for the limited amount of cancer material. The kit prototypes will be validated on clinical samples. A kit for following patient during treatment is also developed.
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Network
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Eurostars
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Call
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Eurostars Cut-Off 10
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Project partner
