Quantitative analysis of HER2, HER3, and γH2AX expression on circulating tumor cells for pharmacodynamic measurement in clinical trials

Repeat tissue biopsies are often impractical for tracking how a therapy is working, so this AACR 2025 poster develops circulating tumor cell assays that quantify HER2, HER3, and γH2AX protein expression from a blood draw for pharmacodynamic measurement in clinical trials.

Presented by RareCyte.

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• Three single-biomarker CTC assays — one each for HER2, HER3, and γH2AX — were analytically validated on cell lines spiked into healthy donor blood. On these model CTCs, sensitivity was 100% for HER2, 88.1% for HER3, and 91.9% for γH2AX, with specificity of 97.7%, 96.0%, and 96.7% respectively — analytical figures on spiked control cells, not clinical performance in patients.
• Every assay proved reproducible, with all coefficients of variation under 20%. Inter-stainer-run precision ranged from 8.0% (HER2) to 18.4% (γH2AX) across three independent stainer runs, and intra-run repeatability held within 3.8–12.1% across five control slides in a single run.
• The HER2 assay was tested on 16 cell lines with a range of HER2 expression, distinguishing the known IHC scores of 0, 1+, 2+, and 3+. All three assays have been deployed in clinical trials as pharmacodynamic biomarkers, and each single-biomarker assay can be extended to a dual readout by adding one custom marker of interest to the same CTC.