Data from Integrated Analysis of Multiple Biomarkers from Circulating Tumor Cells Enabled by Exclusion-Based Analyte Isolation

• DOI: 10.1158/1078-0432.c.6525912
• Publication Date: 2023-04-01T07:40:54Z
• Authors: Jamie M. Sperger; Lindsay N. Strotman; Allison Welsh; Benjamin P. Casavant; Zachery Chalmers; Sacha Horn; Erika Heninger; Stephanie M. Thiede; Jacob Tokar; Benjamin K. Gibbs; David J. Guckenbe...; Lakeesha Carmichael; Scott M. Dehm; Philip J. Stephens; David J. Beebe; Scott M. Berry; Joshua M. Lang

<div>Abstract<p><b>Purpose:</b> There is a critical clinical need for new predictive and pharmacodynamic biomarkers that evaluate pathway activity in patients treated with targeted therapies. A microscale platform known as VERSA (versatile exclusion-based rare sample analysis) was developed to integrate readouts across protein, mRNA, DNA circulating tumor cells (CTC) comprehensive analysis of the androgen receptor (AR) signaling pathway.</p><p><b>Experimental Design:</b> Utilizing preparation principles, handheld chip perform CTC capture, enumeration, quantification, subcellular localization proteins extraction mRNA DNA. This technology validated integrated endpoints cell lines cohort castrate-resistant prostate cancer (CRPC) AR-targeted therapies chemotherapies.</p><p><b>Results:</b> The analyze AR protein expression, nuclear localization, gene expression targets. When applied patients, radiographic progression predicted by presence multiple splice variants canonical pathway. identified phenotypic heterogeneity. Next-generation sequencing FoundationOne panel detected copy number changes point mutations. Longitudinal CTCs acquisition during treatments chemotherapy.</p><p><b>Conclusions:</b> Complex mechanisms resistance therapies, RNA, DNA, endpoints, exist CRPC can be quantified CTCs. Interrogation revealed distinct patterns relevant serve <i>Clin Cancer Res; 23(3); 746–56. ©2016 AACR.</i></p></div>