Development of a novel personalized medicine platform using apheretically isolated circulating tumor cells to assess drug responsiveness in prostate cancer

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Project Summary Metastatic prostate cancer is a notoriously heterogeneous disease that is difficult to treat. The five-year survival rate has not improved over the past twenty-five years and the median survival rate for those diagnosed with metastatic castration resistant prostate cancer (mCRPC) is only 15-36 months. Precision medicine has the potential to improve mCRPC outcomes. Transciptomic sequencing of circulating tumor cells (CTCs) can provide important information regarding metastatic disease and is an attractive alternative to serial biopsies of metastatic lesions as biopsies are difficult for sick patients to endure and they do not always yield a viable tumor specimen for analysis. Metastatic lesions are often established from CTC progenitors seeding a distant site through the bloodstream or lymphatic system. Current methods for extracting 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 obtaining 10 CTCs per procedure. Thus, there remains a major unmet need to improve the technologies that can identify and isolate CTCs from the bloodstream of patients with metastatic disease. Astrin Biosciences will improve upon current CTC technologies by developing a novel individualized medicine platform that uses apheresis to isolate CTCs. A Machine Learning classifier built upon quantitative holograms intelligently identifies and filters large numbers of CTCs that are viable for ex vivo drug testing. The Astrin Biosciences platform can capture and analyze 10,000 CTCs with a single procedure, providing an opportunity for comprehensive representation of the heterogeneity of mCRPC. This process allows for improved determination of activated pathways that will help infer precision drug targets that can be tested on the patient’s own cancer cells. Knowledge of the optimal course of therapy prior to systemic drug administration will improve response to therapy at a lower cost to the system. This proposal thus aims to do the following: 1) assess feasibility for aphaeretic extraction of large numbers of CTCs from patients with mCRPC and 2) complete comparative profiling and ex vivo viability testing of cultured CTCs. This platform could shift the current paradigm of metastatic prostate cancer treatment and offer a novel approach to improve the poor 5-year survival rate of mCRPC.