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Use of a genetic signature diagnostically to evaluate treatment strategies for prostate cancer

A prostate cancer, gene technology, applied in disease diagnosis, microbial determination/examination, instruments, etc., can solve problems such as different responses

Pending Publication Date: 2018-07-17
DECIPHER BIOSCI INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, stage-matched tumors grouped by histological or molecular subtype may respond differently to the same treatment regimen

Method used

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  • Use of a genetic signature diagnostically to evaluate treatment strategies for prostate cancer
  • Use of a genetic signature diagnostically to evaluate treatment strategies for prostate cancer
  • Use of a genetic signature diagnostically to evaluate treatment strategies for prostate cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0239] Example 1: Development and evaluation of a genomic classifier to predict hormone therapy failure.

[0240] A genomic classifier for predicting hormone therapy failure in prostate cancer subjects was developed as follows. Neuroendocrine prostate cancer (NEPC) can be less sensitive or even resistant to androgen deprivation therapy (ADT), one of the main treatment options for locally advanced, recurrent and metastatic prostate cancer. We collected a set of 1,557 genes to construct a genomic classifier that predicts response to ADT.

[0241] A total of 529 subjects' prostate cancer expression profiles from formalin-fixed paraffin-embedded (FFPE) tissues were analyzed from the Decipher GRID database and used as a signature for developing androgen withdrawal therapy (ADT) resistance ( ARS) training set. The training data was collected from a nested case-control design cohort in the Mayo Clinic tumor registry, which was previously used to develop the Decipher prostate cancer...

example 2

[0254] Example 2: Systems biology of the ARS gene

[0255] Functional characterization of genes performed in the ARS model revealed that the genes are involved in multiple biological pathways and biological processes involved in cancer progression and neuronal development ( Figure 5 ). Several genes such as NSMCE4A, FOXM1, TFAP, GABRB3 and ATF5 are associated with DNA damage response and apoptosis signaling pathways. In addition, some of the genes have evidence of involvement in androgen signaling. For example, HEY2 has been reported to specifically inhibit AR-dependent transcriptional activity (Villaronga et al. (2008) Curr. Cancer Drug Targets 8(7):566-580). Other ARS genes, including RRM2 and CRISP2, play a role in the cell cycle and cell proliferation. RRM2 plays a role in the proliferation, invasion of prostate cancer, and when it is overexpressed, it is associated with the resistance of other cancers to gemcitabine and platinum-based chemotherapy (Wang et al. (2014) ...

Embodiment 3

[0256] Example 3: Independent Validation of ARS Predicting Hormone Therapy Failure After Adjuvant Hormone Therapy

[0257] The ARS model was validated in an independent cohort from Mayo Clinic II (n=233) (Karnes et al. (2013) J. Urol. 190(6):2047-2053; incorporated herein by reference). The cohort was a case cohort design with 101 treated subjects, 51 subjects with metastases, and 132 subjects who did not receive ADT (which had 24 subjects with metastases) (Karnes et al. , ibid.). The same tissue selection and sample processing as in Example 1 was applied. In this independent validation, ARS had a 10-year survival c-index of 0.69 (95% CI 0.59-0.78) in subjects treated with adjuvant ADT compared to untreated subjects The 10-year survival c-index was 0.45 (95% CI 0.29-0.61) ( Image 6 ). Treated subjects with metastases had high scores compared to untreated subjects with baseline scores. These results suggest that treated subjects with higher ARS scores are prone to treatme...

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Abstract

Methods, compositions, and kits for identifying individuals who will be resistant to androgen deprivation therapy for treatment of prostate cancer are disclosed. In particular, the invention relates to an androgen deprivation therapy resistance signature based on expression levels of genes that are differentially expressed between responders and non-responders to androgen deprivation therapy and its use to identify individuals likely to respond poorly or be non-responsive to androgen deprivation therapy, who are in need of treatment for prostate cancer by other methods.

Description

field of invention [0001] The present invention relates to the field of personalized medicine and methods for the diagnosis and treatment of prostate cancer. In particular, the present invention relates to the use of gene signatures to identify subjects in need of prostate cancer treatment who will be resistant to androgen deprivation therapy (ADT). Background of the invention [0002] Cancer is the uncontrolled growth of abnormal cells anywhere in the body. Abnormal cells are called cancer cells, malignant cells, or tumor cells. Many cancerous and abnormal cells that make up cancerous tissue are further identified by the name of the tissue from which the abnormal cells originate (eg, prostate cancer). Cancer cells can proliferate uncontrollably and form cancer cell clumps. Cancer cells can break away from this original cell mass, travel through the blood and lymphatic systems, and lodge in other organs, where they can again repeat the cycle of uncontrolled growth. The p...

Claims

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Application Information

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IPC IPC(8): C12Q1/6886C40B30/04C40B40/06G01N33/48
CPCC12Q2600/106C12Q2600/158G01N33/57434G01N2800/52C12Q1/6886C12Q2600/118C12Q2600/156C40B30/04C40B40/06
Inventor H·阿迪恩阿萨比N·埃尔霍M·艾萨拉发E·达维次奥尼
Owner DECIPHER BIOSCI INC
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