Epic Sciences along with researchers at the MD Anderson Cancer Center (MDA) have recently published their findings on androgen receptor (AR) protein expression in circulating tumor cells (CTCs) in patients with metastatic breast cancer in PLOS One. The publication, the most comprehensive today in characterizing the AR protein in CTCs of patients with breast cancer, identifies subclonal heterogeneity of AR protein.
In recent clinical trials, AR signaling inhibitors, Zytiga® and Xtandi®, approved in metastatic prostate cancer, have demonstrated potential benefits in a portion of women with metastatic breast cancer. However, current tools to identify patients who may benefit from AR signaling inhibitors are invasive and suffer from accuracy errors in predicting patient response.
In addition to profiling CTCs for AR, estrogen receptor and HER2 biomarkers were also characterized. Protein biomarker heterogeneity was observed in many patients. To support the hypothesis of tumor heterogeneity, single cell genomic profiling identified genomic heterogeneity associated with the protein heterogeneity which has been identified as a resistance marker in cancer.
Representative images of CTC subtypes identified by the Epic Sciences CTC platform
Representative fluorescence microscopy images of subtypes of CTCs identified by the Epic Sciences CTC platform. Blood samples from patients with metastatic breast cancer were deposited on glass slides and stained with a cocktail of DAPI and antibodies against CK, CD45, and AR. After staining, CTCs were detected using a digital pathology algorithm and classified into CTC subtypes on the basis of marker expression profile into CK+ CTCs, CK- CTCs, CTC clusters, and apoptotic CTCs. The top panel shows an AR+CK+ CTC with AR expression localized in the nucleus.
“Subclonal AR protein expression could both identify patients who may resist targeted therapy and at the same time, explain partial response to AR signaling inhibition,” said Ryan Dittamore, chief of medical innovation at Epic Sciences and co-author on the study. “With our academic and biopharma partners, we are expanding our understanding of tumor heterogeneity in metastatic breast cancer to improve tools for patient selection to improve patient survival.”
This study, led by Naoto T. Ueno, M.D., Ph.D., executive director at The University of Texas MDA Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, utilized Epic Sciences non-biased enrichment free platform to characterize CTCs in blood samples. The Epic Sciences platform is currently utilized in more than 175 clinical studies in 12 different cancers.
Source – PR Newswire