Abstract: The disclosure provides a method for detecting prostate specific membrane antigen (PSMA) on circulating tumor cells (CTCs) obtained from a patient afflicted with prostate cancer comprising (a) performing a direct analysis comprising immunofluorescent staining and morphological characterization of nucleated cells in a blood sample obtained from the patient to detect circulating tumor cells (CTC), and (b) determining the number of CTCs expressing PSMA.

Abstract: The present invention provides a method of identifying a metastatic castration resistant prostate cancer (mCRPC) patient with an improved response to taxane therapy compared to androgen receptor (AR) targeted therapy comprising (a) performing a direct analysis comprising immunofluorescent staining and morphological characterization of nucleated cells in a blood sample obtained from the patient to generate circulating tumor cell (CTC) data, wherein the analysis comprises detecting the presence of an Androgen Receptor Variant 7 (AR-V7) in said cells, and (c) evaluating the CTC data to identify a mCRPC patient with an improved response to taxane therapy compared to ARS-directed therapy therapy.

Abstract: The present invention describes a method for detecting NEPC in a patient afflicted with prostate cancer comprising (a) performing a direct analysis comprising immunofluorescent staining and morphological characterization of nucleated cells in a blood sample obtained from the patient to detect circulating tumor cells (CTC), and (b) determining presence or absence of a CTC subpopulation associated with NEPC comprising detecting a measurable feature of each biomarker in a panel of morphological and protein biomarkers, wherein the presence of the CTC subpopulation associated with NEPC is indicative of NEPC. In other embodiments, the biomarkers for the CTC subpopulation associated with NEPC comprise small size, absence of Androgen Receptor (AR?), and presence of nucleoli (nucleoli+). In additional embodiments, the methods of the invention further comprise molecular analysis of the CTCs.

Abstract: The disclosure provides a method of detecting heterogeneity of disease in a 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 identify and enumerate circulating tumor cells (CTC); (b) isolating the CTCs from the sample; (c) individually characterizing genomic parameters to generate a genomic profile for each of the CTCs, and (d) determining heterogeneity of disease in the cancer patient based on the profile. In some embodiments, the cancer is prostate cancer. In some embodiments, the prostate cancer is hormone refractory.

Abstract: The disclosure provides a method of identifying a cell type, or the presence or absence of a cell type, associated with response to abiraterone or enzalutamide in a cancer patient, comprising (a) performing a direct analysis comprising immunofluorescent staining and morphological characterization of nucleated cells in a blood sample obtained from the patient to identify and enumerate circulating tumor cells (CTC); (b) isolating the CTCs from the sample; (c) individually characterizing parameters to generate a profile for each of the CTCs, and (d) identifying a biomarker CTC, wherein presence or absence of the biomarker CTC indicates a responsiveness in the patient to abiraterone or enzalutamide.

Abstract: The disclosure provides methods correlating intra-patient genomic heterogeneity of single CTCs with phenotypic heterogeneity in each of a population of prostate cancer (PCa) patients.

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.

Abstract: The disclosure provides a method of predicting resistance to androgen receptor (AR) targeted therapy in a prostate cancer patient comprising (a) performing a direct analysis comprising immunofluorescent staining and morphological characterization of nucleated cells in a blood sample obtained from the patient to identify circulating tumor cells (CTCs), and (b) based on said direct analysis further determining the presence of a biomarker signature that is predictive of resistance to AR targeted therapy in the prostate cancer patient, wherein the biomarker signature comprises CK+, AR+, nucleoli+ CTCs in a subpopulation of said CTCs.

Abstract: The disclosure provides a method of detecting heterogeneity of disease in a 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 identify and enumerate circulating tumor cells (CTC); (b) isolating the CTCs from the sample; (c) individually characterizing genomic parameters to generate a genomic profile for each of the CTCs, and (c) determining heterogeneity of disease in the cancer patient based on the profile. In some embodiments, the cancer is prostate cancer. In some embodiments, the prostate cancer is hormone refractory.

Abstract: The disclosure provides a method for detecting prostate specific membrane antigen (PSMA) on circulating tumor cells (CTCs) obtained from a patient afflicted with prostate cancer comprising (a) performing a direct analysis comprising immunofluorescent staining and morphological characterization of nucleated cells in a blood sample obtained from the patient to detect circulating tumor cells (CTC), and (b) determining the number of CTCs expressing PSMA.

Abstract: The disclosure provides methods for detecting circulating endothelial cells (CECs) that mimic CTCs with respect to aspects of their immuno fluorescent staining and with respect to aspects of their morphological characteristics (CTC mimics). The present disclosure is based, in part, on the unexpected discovery that CTC mimics can be detected in non-enriched blood samples among CTC candidate cells. The present disclosure is further based, in part, on the discovery that CTC mimics can be detected in non-enriched blood samples by combining the detection of one or more immunofluorescent markers in the nucleated cells of a non-enriched blood sample with an assessment of the morphology of the nucleated cells.

Abstract: The present invention describes a method for detecting castration-resistant prostate cancer (CRPC) in a patient afflicted with prostate cancer comprising (a) performing a direct analysis comprising immunofluorescent staining and morphological characterization of nucleated cells in a blood sample obtained from the patient to detect circulating tumor cells (CTC), (b) determining prevalence of a CTC subpopulation associated with CRPC comprising detecting a measurable feature of each biomarker in a panel of morphological and protein biomarkers, and (c) comparing the prevalence of said CTC subpopulation to a predetermined threshold value, wherein the prevalence of the CTC subpopulation associated with CRPC above said predetermined threshold value is indicative of CRPC. In some embodiments, the CTC subpopulation associated with CRPC comprises CK? CTCs. In some embodiments, the CTC subpopulation associated with CRPC comprises small CTCs.

Abstract: The present invention describes a method for detecting castration-resistant prostate cancer (CRPC) in a patient afflicted with prostate cancer comprising (a) performing a direct analysis comprising immunofluorescent staining and morphological characterization of nucleated cells in a blood sample obtained from the patient to detect circulating tumor cells (CTC), (b) determining prevalence of a CTC subpopulation associated with CRPC comprising detecting a measurable feature of each biomarker in a panel of morphological and protein biomarkers, and (c) comparing the prevalence of said CTC subpopulation to a predetermined threshold value, wherein the prevalence of the CTC subpopulation associated with CRPC above said predetermined threshold value is indicative of CRPC. In some embodiments, the CTC subpopulation associated with CRPC comprises CK? CTCs. In some embodiments, the CTC subpopulation associated with CRPC comprises small CTCs.

Abstract: The present invention provides a method of identifying a metastatic castration resistant prostate cancer (mCRPC) patient with an improved response to taxane therapy compared to androgen receptor (AR) targeted therapy comprising (a) performing a direct analysis comprising immunofluorescent staining and morphological characterization of nucleated cells in a blood sample obtained from the patient to generate circulating tumor cell (CTC) data, wherein the analysis comprises detecting the presence of an Androgen Receptor Variant 7 (AR-V7) in said cells, and (c) evaluating the CTC data to identify a mCRPC patient with an improved response to taxane therapy compared to ARS-directed therapy therapy.

Abstract: The disclosure provides a method of detecting heterogeneity of disease in a 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 identify and enumerate circulating tumor cells (CTC); (b) isolating the CTCs from the sample; (c) individually characterizing genomic parameters to generate a genomic profile for each of the CTCs, and (d) determining heterogeneity of disease in the cancer patient based on the profile. In some embodiments, the cancer is prostate cancer. In some embodiments, the prostate cancer is hormone refractory.

Abstract: The disclosure provides a method of detecting heterogeneity of disease in a 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 identify and enumerate circulating tumor cells (CTC); (b) isolating the CTCs from the sample; (c) individually characterizing genomic parameters to generate a genomic profile for each of the CTCs, and (c) determining heterogeneity of disease in the cancer patient based on the profile. In some embodiments, the cancer is prostate cancer. In some embodiments, the prostate cancer is hormone refractory.

Abstract: The disclosure provides methods for automated characterization of circulating tumor cells (CTCs), for example using automated tissue strainers. In specific examples, such methods permit characterizing a prostate cancer sample by simultaneously or contemporaneously detecting ERG rearrangements and PTEN deletions in the same CTC. Also provided are kits that can be used with such methods.

Abstract: The disclosure provides methods correlating intra-patient genomic heterogeneity of single CTCs with phenotypic heterogeneity in each of a population of prostate cancer (PCa) patients.

Abstract: The disclosure provides a method of predicting resistance to androgen receptor (AR) targeted therapy in a prostate cancer patient comprising (a) performing a direct analysis comprising immunofluorescent staining and morphological characterization of nucleated cells in a blood sample obtained from the patient to identify circulating tumor cells (CTCs), and (b) based on said direct analysis further determining the presence of a biomarker signature that is predictive of resistance to AR targeted therapy in the prostate cancer patient, wherein the biomarker signature comprises CK+, AR+, nucleoli+CTCs in a subpopulation of said CTCs.

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 (b) 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. Further disclosed are the panel of traditional and non-traditional CTC biomarkers for the methods.