Metastatic prostate cancer is a notoriously heterogeneous disease that is difficult to treat. Thefive-year survival rate has not improved over the past twenty-five years and the median survivalrate for those diagnosed with metastatic castration resistant prostate cancer (mCRPC) is only15-36 months. Precision medicine has the potential to improve mCRPC outcomes.Transciptomic sequencing of circulating tumor cells (CTCs) can provide important informationregarding metastatic disease and is an attractive alternative to serial biopsies of metastaticlesions as biopsies are difficult for sick patients to endure and they do not always yield a viabletumor specimen for analysis. Metastatic lesions are often established from CTC progenitorsseeding a distant site through the bloodstream or lymphatic system. Current methods forextracting and analyzing CTCs from the bloodstream are clinically limited as they are expensive,inefficient, and do not yield enough CTCs to capture actionable biomarkers, often only obtaining10 CTCs per procedure. Thus, there remains a major unmet need to improve the technologiesthat can identify and isolate CTCs from the bloodstream of patients with metastatic disease.Astrin Biosciences will improve upon current CTC technologies by developing a novelindividualized medicine platform that uses apheresis to isolate CTCs. A Machine Learningclassifier built upon quantitative holograms intelligently identifies and filters large numbers ofCTCs that are viable for ex vivo drug testing. The Astrin Biosciences platform can capture andanalyze 10,000 CTCs with a single procedure, providing an opportunity for comprehensiverepresentation of the heterogeneity of mCRPC. This process allows for improved determinationof activated pathways that will help infer precision drug targets that can be tested on thepatient's own cancer cells. Knowledge of the optimal course of therapy prior to systemic drugadministration will improve response to therapy at a lower cost to the system. This proposal thusaims to do the following: 1) assess feasibility for aphaeretic extraction of large numbers of CTCsfrom patients with mCRPC and 2) complete comparative profiling and ex vivo viability testing ofcultured CTCs. This platform could shift the current paradigm of metastatic prostate cancertreatment and offer a novel approach to improve the poor 5-year survival rate of mCRPC.
Public Health Relevance Statement: Project Narrative
Transcriptomic sequencing of circulating tumor cells (CTCs) in patients with metastatic prostate
cancer provides important information regarding metastatic disease and is an attractive
alternative to serial biopsies. Astrin Biosciences will harness the power of transcriptomics by
developing an aphaeretic platform that can isolate and analyze 10,000 CTCs from a single
procedure to allow for ex vivo viability testing with targeted drug candidates. This platform can
shift the paradigm of how metastatic cancer is currently treated to improve progression-free
survival rates in those suffering from metastatic disease.
Project Terms: | <µfluidic> | | | | | | | | | | | | 