Use of markers in the diagnosis and treatment of prostate cancer

a prostate cancer and marker technology, applied in the field of prostate cancer diagnosis and treatment, can solve the problems of erectile dysfunction, difficult urination, aggressive prostate cancer, etc., and achieve the effects of increasing reducing the risk of prostate cancer, and increasing the predictive valu

Inactive Publication Date: 2014-02-06
BERG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent text describes methods for predicting an increased risk of developing prostate cancer by detecting specific markers in a biological sample, such as filamin B, LY9, and keratin 19. These markers are compared to a normal control sample and an increase in their level indicates an increased risk of prostate cancer. The methods also involve detecting the level of prostate specific antigen (PSA) in the sample and comparing it to a normal control level. An increase in the level of the markers in combination with an increase in PSA level has greater predictive value of progression of prostate cancer than any single marker alone. The methods can help in early diagnosis and management of prostate cancer.

Problems solved by technology

Oncological disorders, such as cancer, are presently one of the leading causes of death in developed nations and is a serious threat to modern society.
However, there are cases of aggressive prostate cancers.
Prostate cancer may cause pain, difficulty in urinating, problems during sexual intercourse, or erectile dysfunction.
Further, treatment of prostate cancer may do more harm to the subject than the prostate cancer itself.
Prostate specific antigen (PSA) screening has lead to a significant rise in the number of men diagnosed with prostate cancer with an associated increase in potentially unnecessary biopsies preformed.
Moreover, since men with the condition are typically older, they often die of causes unrelated to the prostate cancer, such as heart / circulatory disease, pneumonia, other unrelated cancers, or old age.

Method used

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  • Use of markers in the diagnosis and treatment of prostate cancer
  • Use of markers in the diagnosis and treatment of prostate cancer
  • Use of markers in the diagnosis and treatment of prostate cancer

Examples

Experimental program
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example 1

Identification of Keratins and Tubulin as Prostate Cancer Markers

[0388]Extracellular Keratins are known to influence the cell proliferation and metastasis of epithelial derived prostate cancers. Androgen refractory prostate cancers exhibit differential expression keratin 8 (K8) when compared to normal tissue. Modulation and degradation of keratins is in turn mediated by mitochondrial generation of Reactive Oxygen Species (ROS). Despite these advances a systematic approach to understanding of keratins and other EC proteins in prostate cancer metastasis and proliferation is lacking. An interrogative systems biology based discovery platform disclosed in WO2012119129 (incorporated herein by reference), and shown schematically in FIG. 1, provides new mechanistic insights into understanding mitochondrial role in behavior of prostate cancer cells. The discovery platform involves discovery across a hierarchy of systems including in vitro human cell based models and human serum samples from ...

example 2

Identification of Filamin B as a Prostate Cancer Marker

[0392]An interrogative systems biology based discovery platform was used to obtain mechanistic insights into understanding mitochondrial role in behavior of prostate cancer cells. The Platform technology, which is described in detail in WO2012119129, involves discovery across a hierarchy of systems including in vitro human cell based models and human serum samples from prostate cancer patients and downstream data integration and mathematical modeling employing an Artificial Intelligence (AI) based informatics module.

[0393]The results provided herein demonstrate the modulation of filamin B and LY9, and potential causal association in androgen refractory prostate cancer that was inferred using the Platform technology. The application provides potential mechanisms of filamin B and LY9 regulation in response to modulation of mitochondrial function was deciphered by the Platform technology and provides validation of the markers in pa...

example 3

Validation of Filamin B as a Prostate Cancer Marker in Human Samples

[0396]Having identified filamin B as a prostate cancer marker using the platform technology, human serum samples from normal subjects and subjects with prostate cancer were used to confirm filamin B as a prostate cancer marker.

[0397]Specifically, human serum samples were procured from a commercial vendor that sources human serum. Twenty samples were from normal donors and 20 samples were from patients diagnosed with prostate cancer. Prostate cancer samples were from patients with different prognosis and aggressiveness of cancers reported. Clinical characteristics of the subjects are provided in the table.

Prostate CancerControl GroupMedian Age61 (47-86)58 (45-72)EthnicityCaucasian75%85%African American15%10%Hispanic10% 5%Tumor StageStage I20%Stage II35%Stage III 5%Stage IV40%

[0398]Commercially available ELISA tests for filamin B and PSA were procured from commercial source. The assays were performed using the manufac...

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PUM

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Abstract

The invention provides method for diagnosis, monitoring, and prognosis of prostate cancer using one or more of keratin 4, keratin 7, keratin 8, keratin 15, keratin 18, keratin 19, tubulin-beta 3, filamin B, and LY9, and PSA. The invention provides kits for practicing the methods of the invention.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority to U.S. Provisional Application Ser. No. 61 / 665,201, filed Jun. 27, 2012; U.S. Provisional Application Ser. No. 61 / 672,090, filed Jul. 16, 2012; U.S. Provisional Application Ser. No. 61 / 673,094, filed Jul. 18, 2012; U.S. Provisional Application Ser. No. 61 / 702,523, filed Sep. 18, 2012, and U.S. Provisional Application Ser. Nos. 61 / 718,064, 61 / 718,080, and 61 / 718,081 all filed on Oct. 24, 2012. Each of the applications is incorporated herein by reference in its entirety.SEQUENCE LISTING[0002]The instant application contains a Sequence Listing which has been submitted in ASCII format via EFS-Web and is hereby incorporated by reference in its entirety. Said ASCII copy, created on Jun. 25, 2013, is named 119992-06604_SL.txt and is 461,537 bytes in size.FIELD OF THE INVENTION[0003]The invention relates to treatment, prevention, reduction, diagnosis, monitoring, and prognosis of abnormal prostate states, includi...

Claims

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Application Information

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IPC IPC(8): G01N33/68
CPCG01N33/6893C12Q1/6886G01N33/57434G01N2800/50G01N2800/56C12Q2600/158C12Q2600/118C12Q2600/106G01N2333/47G01N2333/4742
Inventor NARAIN, NIVEN RAJINSARANGARAJAN, RANGAPRASADVISHNUDAS, VIVEK K.
Owner BERG
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