Getting More from Less: Multi-omic Capture and Analysis from Patient Samples

DESCRIPTIONprovided by applicantPersonalized medicine is predicated on having sufficient patient specific information to provide a diagnosis specific to that patientGenomicse gnext generation sequencingis now being adopted into clinical practice and is enabling improvements in patient specific care particularly in cancerHoweversequence information alone will not be sufficient to realize the full potential of personalized medicineIf we examine prostate cancermore than half of patients do not benefit from new anti cancer therapies such as Abiraterone and Enzalutamide and nearly all patients who initially benefit develop resistance withinyearsYetfor the clinician the treatment decisions are largely guesswork as he she has little quantitative mechanistic data to guide treatment choicesImportantlyprostate cancer is driven in large part by the Androgen ReceptorARincluding ligand binding and translocation from the cytoplasm to the nucleus activating a transcriptional program critical to tumorigenesisMultiple drugs are currently available that prevent nuclear translocation of the AR via different mechanismsbut sequencing alone will be insufficient to accurately guide therapy choice and to monitor the development of resistancesimilar scenarios exist in other cancers and other diseasesPredicting and monitoring targeted therapies requires orthogonal multi omici eproteingenomicgene expressionendpointsCirculating tumor cellsCTCshave great potential as an accessible sample and many technologies are being developed for CTC analysisbut none have the ability to perform multi omic analysis from a single sampleThis proposal addresses these issues by leveraging and advancing Exclusion based Sample PreparationESPto enable the rapid and efficient isolation of multiple analytescellsproteins RNADNAfrom a single precious sample with high recovery and purityTo efficiently move this platform into the clinicwe have signed licensing agreements with Gilson and Foundation Medicinerecently acquired by Rocheindustry leaders in instrumentation manufacturingand advanced cancer diagnostics clinical laboratory test development respectivelyAdditionally our clinical collaboratorDrLangUniversity of Wisconsinwill enable us to directly demonstrate the clinical efficacy of our multi omic approach during the SBIR proposal periodusing advanced prostate cancer as a clinical modelAs illustrated by the AR model systemassays capable of measuring multi omic biomarkers would enable clinicians to make more informed decisions about what type of therapy to use and when to use it for patients with progressive diseaseinforming both choice of initial treatment as well as when to switch therapy as resistance occursWe have chosen to submit a Fast Track SBIR Proposal and have addressed the Fast Track requirements of clear Phase I goals and clear evidencee glettersof additional funding and resource commitments that significantly enhance the likelihood of successful commercialization