(ChemotherapyAdvisor) – Androgen receptor (AR) reactivation patterns in castration-resistant prostate cancer can be measured in real time and might prove to be predictive of patient outcomes following androgen blockade, according to a study published in Cancer Discovery.
“Acquired resistance to first-line hormonal therapy in prostate cancer is heterogeneous in the extent of AR pathway reactivation,” reported senior author Daniel A. Haber, MD, PhD, director of the Massachusetts General Hospital Cancer Center in Boston, and coauthors. “Measurement of pre- and posttreatment AR signaling within CTCs may help target such treatments to patients most likely to respond to second-line therapies.”
The authors employed a recently-developed microfluidic chip to capture circulating tumor cells (CTCs) and measure “AR-signaling readouts” before and after therapeutic interactions, they wrote.
The CTC-chip assay measures the expression of the androgen receptor-regulated genes for prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA).
“Single-cell immunofluorescence analysis revealed predominantly ‘AR-on’ CTC signatures in untreated patients, compared with heterogeneous (‘AR-on, AR-off, and AR-mixed’) CTC populations in patients with CRPC,” they reported. “Initiation of first-line ADT induced a profound switch from ‘AR-on’ to ‘AR-off’ CTCs, whereas secondary hormonal therapy in CRPC resulted in variable responses.”
Systemic androgen declines might suppress metastatic tumor cells with reactivated AR signaling, they reported.
“Four of 17 (24%) patients with CRPC treated with abiraterone acetate had a 50% or more decline in the percentage of ‘AR-on’ CTCs within 2 to 5 weeks of therapy,” they wrote.
The study proves that is possible to noninvasively monitor the androgen receptor signaling pathway “in real time” among patients with metastatic prostate cancer, the authors concluded.
“Although this assay has potential as a promising biomarker, it requires validation in larger prospective studies of patients with prostate cancer undergoing second-line hormonal therapy,” they cautioned. “Individualization of second-line treatments in metastatic prostate cancer will be essential for therapeutic success, given the evident tumor cell heterogeneity that accompanies the emergence of resistance to initial androgen deprivation.”