LaGrange Scientific, LLC — Department of Health and Human Services SBIR Phase I: 102

Description

ABSTRACTThe goal of this Phase I SBIR is to address the absence of measureable and targeted metabolite biomarkers in clear cell renal cell carcinomaccRCCtissues that can predict disease metastasisAn estimatedAmericans were diagnosed with kidney cancer inand approximatelydied as a result of ccRCCprimarily due to metastasis of the cancerUltimatelywe seek to identify those patients with more aggressive renal cancers that might benefit from more aggressive treatmentPatients with indolent ccRCC may choose less aggressive treatment while those with a greater risk of metastasis may elect adjuvant therapy that may include drug treatmentsThere are no diagnostic tests that predict post surgical disease progression on the marketOur methodology will utilize novel liquid chromatographyLCand mass spectrometryMSmethods developed by our collaboratorsalong with several new methods we developed that will greatly increase quantitative accuracy and robustnessThis will address a series of issues that have plagued the development of a reliable biomarker panel for the diagnosis of renal cancer progression and metastasisA major problem with metabolomic studies to date is that the heterogeneity of cancer tissues is frequently overlookedThusan important part of our approach includes normalizationcalibrationand quantitation of metabolites in both discovery and targeted modesSpecificallyour method allows for the analysis of metabolites in small biopsies and will permit histopathology to be performed on exactly the same tissueWhereas normalization and quantitation are usually addressed after data has been acquiredi epostacquisitionwe add pre acquisition normalizationwhich will ensure that equal amounts of sample are injected for MSOur use of chemical labeling and sample normalization will minimize the effects of ion suppressionsignal saturationcolumn contaminationagingand instrument performance driftEssentiallythe day to day and lab to lab variabilitywhich frequently affect MSwill be minimizedIn this proposalwe will utilize the Eastern Virginia Medical School Biorepository PROBE cohortwhich houses overrenal tumors and associated clinical dataincluding treatmentvital statusimaging dataand longitudinal follow up after primary tumor resectionThe database accompanying the Biorepository is regularly updatedallowing us to identify those whoprogressedvsthose who are termednon progressorsFor this Phase I proof of concept studytissues frompatients that developed metastasis will be analyzed and compared topatients that did not develop metastasisnpatientsAll tumor tissuesprimary and metastaticwill be paired withnormaltumor adjacent tissue from clear marginsIn additionlarger numbers of patients in the cohort will be analyzed using available histopathological and staging data as surrogates for clinical outcomeA side benefit to this study is the prospective addition to our ccRCC bank for Phase II studies PROJECT NARRATIVE Our goal is to develop an FDA approved prognostic test for metastatic clear cell renal cell carcinomaccRCCThe development of a specific panel of metabolic biomarkers will be associated with progression from primary tumor to a disseminated metastatic disease stateUltimatelywe will develop a laboratory testing service for characteristics of ccRCC that are correlated with and predictive of progression to metastasis in this high risk patient populationThis will assist the physician surgeon in facilitating intervention prior to metastasisWe envision this test being run by a specialized laboratory using our protocols at LAGRANGE SCIENTIFICor at a licensed laboratoryAt an estimated $per testwe envision a $million yr marketbased on approximatelysamples per year from patients with potentially metastatic ccRCC