- Email: [email protected]
How biomarker validation platforms can accelerate “bench to bedside” efficiency
Abstracts
remain incurable, with a median survival of 12 months, and less than 5% of patients alive at 5 years. The lecture will present WIN Consortium efforts to significantly improve the clinical outcome of lung cancer patients: A major portion is international collaboration to improve molecular profiling and data management and design of innovative trials, driven by new biomarker based platforms, tools and strategies. Combination of targeted therapies: The key feature of future therapies in metastatic NSCLC, is switching from current monotherapies to combinatorial modes, as only way to fight against secondary resistance that occurs in all patients. This switch will need the identification and validation of new tools to match individually the patient's tumor biology profile to the most appropriate combination of therapies. The main limitations of current biomarker and mainly companion diagnostics (Cdx) are: a) multiplicity of drugs that require a large number of tests (and different technologies) to be performed on limited amount of biological samples. b) inability to prioritize the best therapeutic options for each individual patient.
The lecture will present the Simplified Interventional Mapping System (SIMS), a Systems Biology based novel generation of multiplex combinatorial Cdx which provides biological support to prioritize and to select the classes of drugs that are predicted to be most effective at the individual patient level. The example used is metastatic Non-Small Cell Lung Carcinoma (NSCLC), but the method applies to any solid tumor. SIMS is based on the use of dual biopsies in order to compare tumor with its histologically matched normal tissue from the same patients. SIMS algorithm integrates data of DNA sequencing, CNV, and the differential expression of mRNA and miRNA between tumor and matched normal tissue from 121 NSCLC patients. SIMS converts thousands of genomic and transcriptomic measurements into a simple and actionable result (a 1 to 10 score) that may be usable by physicians to select the optimal drug or drugs' combinations therapy. One of the most interesting hypothesis being the tri-therapy approaches, following the historical success in AIDS. Comparing tumor and normal tissue biopsies has proven feasible in the ongoing WINTHER trial (NCT01856296) SIMS outlines novel therapeutic possibilities by focusing on pertinent classes of targeted biotherapeutics to be used in appropriate combinations, and is a
S3
novel generation of combinatorial multiplex companion test enabling to match patients to drugs. doi:10.1016/j.mgene.2018.05.031
How biomarker validation platforms can accelerate “bench to bedside” efficiency Catherine Larue Integrated BioBank of Luxembourg (IBBL), Luxembourg E-mail address: [email protected] Abstract After a huge hype for innovative biomarkers when clinically useful biomarkers such as troponin, procalcitonin, PSA, etc. appeared, after considerable amounts of investments in H2020 “OMICS” calls or IMI consortia such as “safety” biomarkers, it is time for disappointment on both sides of academic research and health-related bioindustry. Every year, thousands of biomarkers are published through an abundant literature, but less than 5% of those are used clinically mainly because they are not properly validated. This issue has led to particularly in Europe, a delay in using new biomarkers e.g. in translational medicine, to a misunderstanding by academic researchers of the needs for investigating the biomarker robustness further and deeper, to a certain degree of risk adversity by Pharma or IVD industry and globally to a decrease of the impact of our research & innovation. By conducting pre-analytical and analytical validations, clinical verification to get the performance of a biomarker validated in wellqualified clinical sample sets, IBBL biomarker validation platform can provide the academic researcher with a full report and scientific arguments, and therefore better promote his discovery to industry. Building bridges between academic research and health industry, such as biomarker validation platforms, can dramatically help European research to be more efficient, more productive, particularly through a light of translational applications where bench to bedside efficiency must be quickly achieved. doi:10.1016/j.mgene.2018.05.032
remain incurable, with a median survival of 12 months, and less than 5% of patients alive at 5 years. The lecture will present WIN Consortium efforts to significantly improve the clinical outcome of lung cancer patients: A major portion is international collaboration to improve molecular profiling and data management and design of innovative trials, driven by new biomarker based platforms, tools and strategies. Combination of targeted therapies: The key feature of future therapies in metastatic NSCLC, is switching from current monotherapies to combinatorial modes, as only way to fight against secondary resistance that occurs in all patients. This switch will need the identification and validation of new tools to match individually the patient's tumor biology profile to the most appropriate combination of therapies. The main limitations of current biomarker and mainly companion diagnostics (Cdx) are: a) multiplicity of drugs that require a large number of tests (and different technologies) to be performed on limited amount of biological samples. b) inability to prioritize the best therapeutic options for each individual patient.
The lecture will present the Simplified Interventional Mapping System (SIMS), a Systems Biology based novel generation of multiplex combinatorial Cdx which provides biological support to prioritize and to select the classes of drugs that are predicted to be most effective at the individual patient level. The example used is metastatic Non-Small Cell Lung Carcinoma (NSCLC), but the method applies to any solid tumor. SIMS is based on the use of dual biopsies in order to compare tumor with its histologically matched normal tissue from the same patients. SIMS algorithm integrates data of DNA sequencing, CNV, and the differential expression of mRNA and miRNA between tumor and matched normal tissue from 121 NSCLC patients. SIMS converts thousands of genomic and transcriptomic measurements into a simple and actionable result (a 1 to 10 score) that may be usable by physicians to select the optimal drug or drugs' combinations therapy. One of the most interesting hypothesis being the tri-therapy approaches, following the historical success in AIDS. Comparing tumor and normal tissue biopsies has proven feasible in the ongoing WINTHER trial (NCT01856296) SIMS outlines novel therapeutic possibilities by focusing on pertinent classes of targeted biotherapeutics to be used in appropriate combinations, and is a
S3
novel generation of combinatorial multiplex companion test enabling to match patients to drugs. doi:10.1016/j.mgene.2018.05.031
How biomarker validation platforms can accelerate “bench to bedside” efficiency Catherine Larue Integrated BioBank of Luxembourg (IBBL), Luxembourg E-mail address: [email protected] Abstract After a huge hype for innovative biomarkers when clinically useful biomarkers such as troponin, procalcitonin, PSA, etc. appeared, after considerable amounts of investments in H2020 “OMICS” calls or IMI consortia such as “safety” biomarkers, it is time for disappointment on both sides of academic research and health-related bioindustry. Every year, thousands of biomarkers are published through an abundant literature, but less than 5% of those are used clinically mainly because they are not properly validated. This issue has led to particularly in Europe, a delay in using new biomarkers e.g. in translational medicine, to a misunderstanding by academic researchers of the needs for investigating the biomarker robustness further and deeper, to a certain degree of risk adversity by Pharma or IVD industry and globally to a decrease of the impact of our research & innovation. By conducting pre-analytical and analytical validations, clinical verification to get the performance of a biomarker validated in wellqualified clinical sample sets, IBBL biomarker validation platform can provide the academic researcher with a full report and scientific arguments, and therefore better promote his discovery to industry. Building bridges between academic research and health industry, such as biomarker validation platforms, can dramatically help European research to be more efficient, more productive, particularly through a light of translational applications where bench to bedside efficiency must be quickly achieved. doi:10.1016/j.mgene.2018.05.032