The heterogeneity of cancer has long been recognized by differences in cell morphology in a tumor and that the disease is rarely completely eliminated with any systemic therapy. Observations on the differences in cell morphology and now further understanding of single cell genomic profiling has identified that spatial heterogeneity exists at three levels.
Given the complexity of heterogeneity, the least common denominator to understanding tumor heterogeneity is the single tumor cell.
Profile single circulating tumor cells with PhenoGenomic™ profiling:
CTC heterogeneity was hypothesized as a resistance measure to AR Signaling inhibitors (ARSi) and an assumption that patients with high CTC heterogeneity would have improved outcomes utilizing broad based taxane chemotherapies. Indeed CTC heterogeneity demonstrated a therapy interaction as a continuous biomarker of differential therapeutic response in clinical decision making in metastatic prostate cancer. With increasing CTC heterogeneity providing increasing risk of shorten OS with patients treated by ARSi relative to taxane chemotherapy.
Full publication here
Additionally, single CTC subytpes with unique genomic profiles have been identified providing insights into potential resistance mechanism and signaling within phenogenomic profiling
See the poster here
CTC heterogeneity now is a vital tool to assess in a clinical trial setting to understand why some patients may not respond to a targeted therapy which targets a driver alteration within a patients tumor. Questions to understanding CTC heterogeneity longitudinally to understand how tumors evolve during therapy. Additionally, understanding specific cell type sensitivity to therapies in context to single or combination clinical trials.