PSMA-based Microfluidics-Capture of Circulating Prostate Cancer Cells: Study of Microtubule-driven Androgen Receptor Signaling, Gene Fusion, and Gene Expression Profiles with Correlation to Clinical Response to Taxane Therapy—New Capture Technology for Circulating Tumor Cells Supported by PCF-Funding May Prove Useful in Identifying Patients Most Likely to Benefit from Taxotere.

Investigator: David Nanus, MD–Professor of Medicine, Professor of Urology, Mark W. Pasmantier Professor of Hematology and Oncology in Medicine at Weill Cornell Medical College

This project combines, for the first time, an advanced system to capture circulating prostate cancer cells from whole blood with the discovery of a set of biomarkers that may predict sensitivity to Taxotere. While clinical investigations have already shown that Taxotere prolongs survival for advanced prostate cancer patients, this new biotechnology with “liquid biopsies containing circulating prostate cancer cells” could predict which individuals are most likely to respond to this therapy while sparing many from unnecessary side effects.

Progress Report:

Docetaxel (Taxotere) chemotherapy is the standard first line treatment for patients with castrate resistant prostate cancer (CRPC). Data from Dr. Nanus’s laboratory shows that Taxotere works in part by freezing cell movement which promotes cell death, and by inhibiting the androgen receptor, which is considered the most important therapeutic target of prostate cancer. However, some patients do not respond to Taxotere treatment. The challenge is to identify these patients before Taxotere treatment. Circulating tumorcells (CTCs), renegade cells that have broken off of the primary tumor and entered the blood stream, provide researchers with easy access to a patients’ tumor cells. However, in comparison to the number of blood cells in blood these CTCs represent a very small fraction making it difficult to isolate such rare cells. The goal of this award proposal was to develop novel CTC capture technology that can efficiently capture viable CTCs to enable molecular interrogation.

Dr. Nanus and colleagues have successfully designed a CTC capture device capable of isolating ~85% of the total CTCs found in blood. Moreover, the team has also extracted data from these captured CTCs that may inform clinicians about whether a particular patient will be sensitive or insensitive to Taxotere treatment. Dr. Nanus and colleagues are currently testing this device and their CTC analysis protocol for Taxotere sensitivity in a prospective clinical trial at multiple sites including Weill Cornell.