Application of Surface-Enhanced Raman Spectroscopy to Guide Therapy for Advanced Prostate Cancer Patients

Application of Surface-Enhanced Raman Spectroscopy to Guide Therapy for Advanced Prostate Cancer Patients

Publication Date: March 10, 2022


Abstract Image

A critical unmet need for advanced prostate cancer (PCa) patients is optimizing systemic treatments to maximize the benefit for individuals. The response of patients with metastatic castration-resistant prostate cancer (mCRPC) to androgen receptor (AR)-directed hormonal treatments (i.e., enzalutamide and abiraterone) is mediated by the expression of a molecular variant of the androgen receptor called androgen receptor variant 7 (AR-V7). Detection and measurement of AR-V7 in mCRPC patients will lead to more informed PCa treatment. Herein, we demonstrate a quantitative nanoparticle-enhanced sandwich antibody assay for the successful ex vivo measurement of AR-V7 protein in serum from mCRPC patients. The nanoparticles are constructed as extrinsic Raman spectroscopy labels (ERLs), and surface-enhanced Raman spectroscopy (SERS) is used for assay readout. Our approach does not require specialized specimen collection materials, circulating tumor cell enrichment, or pretreatment of serum. Calibration of our assay is accomplished by expressing AR-V7 in an appropriate cell line as AR-V7 is not commercially available. We demonstrate a linear calibration curve from cell lysate and correlate lysate protein with mRNA from cultured prostate cancer cells. Finally, we demonstrate a novel pilot-scale application for clinical use by quantitatively measuring AR-V7 in serum of seven advanced PCa patients. Distinct separation of PCa patients by AR-V7 status (positive or negative) was observed. Together, the presence and amount of AR-V7 in serum offer predictive and prognostic value to inform selection between two classes of systemic treatments (i.e., hormones or taxanes). Triaging patients that are AR-V7-positive to other systemic treatments (e.g., taxane-based chemotherapy) can improve progression-free survival and overall survival.

Cite this: ACS Sens. 2022

The Bird Dogs: Pointing for the Prostate Cancer Cure

For years, Frank Sojonky hid his battle with prostate cancer from the world. But by 2004 he could hide it no longer, as the disease metastasized and began to spread. So when he learned from his oncologist, Dr. Peter Venner, that a chair in prostate cancer research was needed in Alberta, he made his personal goal to raise the funds to do it. That is how the Bird Dogs started and thanks to them and the Alberta Cancer Foundation, Dr. John Lewis and the Alberta Prostate Cancer Research Initiative are making important discoveries to improve the lives of those with prostate cancer.

Watch a video about the Bird Dogs.