Circulating tumor cell diagnostics for identification of resistance to androgen receptor targeted therapies

Abstract

The disclosure provides a method of predicting de novo resistance to androgen receptor (AR) targeted therapy in a tumor of a prostate cancer patient comprising (a) performing a direct analysis comprising immunofluorescent staining and morphological characteristization of nucleated cells in a blood sample obtained from the patient to generate circulating tumor cell (CTC) data, wherein the analysis comprises determining a measurable feature of a panel of traditional and non-traditional CTC biomarkers for de novo resistance to androgen receptor (AR) targeted therapy, and (c) evaluating the CTC data to determine the probability of de novo resistance to the AR targeted therapy in the tumor of the prostate cancer patient. In some embodiments, the immunofluorescent staining comprises staining of nucleated cells comprises pan cytokeratin, cluster of differentiation (CD) 45, diamidino-2-phenylindole (DAPI) and AR. In some embodiments, the biomarkers comprise (1) CTC heterogeneity, (2) frequency of cytokeratin positive (CK+), androgen receptor positive (AR+), nucleoli positive (nucleoli+) CTCs, and (3) frequency of C-terminal truncated CTCs. The method of claim 3, wherein the CTC heterogeneity further comprises biomarkers selected from the group consisting of traditional CTCs, CTC clusters, CK− CTCs, small CTCs, nucleoli+CTCs, CK speckled CTCs and the biomarkers listed in Table 1.

Dependencies are inferred from the claim text.