Circulating tumor cell diagnostics for prostate cancer biomarkers
First Claim
1. A method for detecting progression of prostate cancer to castration-resistant prostate cancer (CRPC) in a 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 detect morphological and protein biomarkers of circulating tumor cells (CTC), wherein the CTCs are present among the nucleated cells subjected to the direct analysis at a frequency of less than 1 in 1,000 nucleated cells;
- (b) determining prevalence of a CTC subpopulation associated with CRPC comprising detecting a measurable feature of each of the biomarkers, wherein determining prevalence of the CTC subpopulation associated with CRPC comprises determining the prevalence of CTCs that have a nuclear size less than 67 μ
m2, and wherein the presence of the CTC subpopulation associated with CRPC is indicative of CRPC, (c) repeating steps (a) and (b), wherein an increase in the prevalence of the presence of the CTC population associated with CRPC indicates progression of prostate cancer to CRPC; and
(d) treating the patient with either (i) androgen deprivation therapy (ADT) if the prevalence has not increased, or (ii) a cancer therapy other than ADT if the prevalence has increased.
2 Assignments
0 Petitions
Accused Products
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. In additional embodiments, the methods of the invention further comprise molecular analysis of the CTCs.
69 Citations
14 Claims
-
1. A method for detecting progression of prostate cancer to castration-resistant prostate cancer (CRPC) in a 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 detect morphological and protein biomarkers of circulating tumor cells (CTC), wherein the CTCs are present among the nucleated cells subjected to the direct analysis at a frequency of less than 1 in 1,000 nucleated cells;
- (b) determining prevalence of a CTC subpopulation associated with CRPC comprising detecting a measurable feature of each of the biomarkers, wherein determining prevalence of the CTC subpopulation associated with CRPC comprises determining the prevalence of CTCs that have a nuclear size less than 67 μ
m2, and wherein the presence of the CTC subpopulation associated with CRPC is indicative of CRPC, (c) repeating steps (a) and (b), wherein an increase in the prevalence of the presence of the CTC population associated with CRPC indicates progression of prostate cancer to CRPC; and
(d) treating the patient with either (i) androgen deprivation therapy (ADT) if the prevalence has not increased, or (ii) a cancer therapy other than ADT if the prevalence has increased. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14)
- (b) determining prevalence of a CTC subpopulation associated with CRPC comprising detecting a measurable feature of each of the biomarkers, wherein determining prevalence of the CTC subpopulation associated with CRPC comprises determining the prevalence of CTCs that have a nuclear size less than 67 μ
Specification