Phosphodiesterase 9A as prostate cancer marker

Patent metadata

Field	Value
Publication number	US-9828604-B2
Application number	US-201013320446-A
Country	US
Kind code	B2
Filing date	May 11, 2010
Priority date	May 12, 2009
Publication date	Nov 28, 2017
Grant date	Nov 28, 2017

Abstract

The present invention relates to phosphodiesterase 9A (PDE9A) for use as a marker for prostate cancer, and the use of PDE9A as a marker for diagnosing, detecting, monitoring or prognosticating prostate cancer or the progression of prostate cancer. The present invention also relates to a composition for diagnosing, detecting, monitoring or prognosticating prostate cancer or the progression of prostate cancer, a corresponding method and immunoassay, a method for diagnosing, monitoring or prognosticating hormone-resistant prostate cancer vs. hormone-sensitive prostate cancer, a corresponding immunoassay, a method of data acquisition, an immunoassay for diagnosing, detecting, monitoring or prognosticating prostate cancer or the progression of prostate cancer, a method of identifying an individual for eligibility for prostate cancer therapy, an immunoassay for stratifying an individual or cohort of individuals with a prostate cancer disease, an immunoassay for stratifying an individual with prostate cancer. The present invention further envisages pharmaceutical compositions and their use for the treatment of prostate cancer, in particular hormone-resistant prostate cancer.

First claim

The invention claimed is:

1. A method for monitoring an expression level of PDE9A in a patient, comprising the steps of
(a) determining a measured expression level of PDE9A in a sample obtained from the patient by using SEQ ID NOs:43 and 47 specific for the cDNA of the PDE9A transcript;
(b) determining the level of expression of two or more reference genes in the sample, at least one being PDE4D5 detected with SEQ ID NO:50;
(c) normalizing the measured expression level of PDE9A to the expression levels of the reference genes; and
(d) comparing the normalized expression level of PDE9A with a predetermined cutoff value, wherein said cutoff value is between 2 and 15 ng/ml, wherein the sample is selected from the group consisting of a prostate tissue sample, a urine sample, a urine sediment sample, a blood sample, a saliva sample, a semen sample, a sample comprising circulating tumor cells, and a sample containing prostate secreted exosomes.

2. The method of claim 1 , wherein said reference genes are selected from β-actin, glycerinaldehyde 3-phosphate dehydrogenase (GAPDH), porphobilinogen deanimase (PBGD), ribosomal protein P1, PDE4D1, PDE4D2, PDE4D3, PDE4D4, PDE4D5, PDE4D6, PDE4D8, and PDE4D9.

3. The method of claim 2 wherein an individual classified or tested with an increased level of PDE9A expression and an increased level of PSA of more than about >2.5 ng/ml up to about 10 ng/ml is identified as suffering from a malignant, hormone sensitive prostate cancer; and wherein an individual classified or tested with a decreased level of PDE9A expression and an increased level of PSA of more than about >10 ng/ml is identified as suffering from hormone resistant prostate cancer.

4. The method of claim 1 , wherein the method comprises the additional step of determining the level of prostate specific antigen (PSA).

Assignees

• Hoffmann Ralf
• Houslay Miles Douglas
• Henderson David James Peter
• Koninklijke Philips Nv
• Univ Glasgow Court

Inventors

• Hoffmann Ralf
• Houslay Miles Douglas
• Henderson David James Peter

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P13/08

  of the prostate · CPC title

• G01N33/57555

  of the prostate · CPC title

• C12Q1/6886

  for cancer (immunoassay for cancer G01N33/575) · CPC title