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

Our First Participant!

Thanks to the participation from men with suspected prostate cancer and men diagnosed with prostate cancer, we will be able to measure if our “tests” can reveal the true nature of prostate cancer and if the tests or biomarkers can diagnose prostate cancer and tell us what cancers are more aggressive.

As part of the Alberta Prostate Registry and Biorepository, patients will be entered into our study, in which blood and other samples are collected over time and their health outcomes are recorded over many years. Patients will follow standard medical advice and care through their doctors. Our team collect biospecimens and information related to general health and cancer behavior over time.

Rather than being frightened by the word ‘cancer’, we want to learn how to predict serious and morbid prostate cancer complications well before they happen, so that we can weigh carefully the pros and cons of available treatments.

In the process, we expect to identify new and important advantage points for better therapies to be developed. The word “cancer” may be scary, but what is truly scary is unawareness.

“It makes me very happy to be able to contribute to find better ways to diagnose prostate cancer.”

- Mr. Garcia