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Methods of identifying and treating poor-prognosis cancers

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Title: Methods of identifying and treating poor-prognosis cancers.
Abstract: The present invention relates generally to methods for identifying cancer patients with a poor prognosis, and to therapeutic modalities for improving prognosis by combating metastasis and abrogating chemoresistance in cancer cells. Embodiments of the present invention provide an objective means of prognostication regarding the long-term outcome of an incident of cancer, breast cancer in particular. Therapeutic modalities include immunotherapy and anti-sense therapy. Prognosis is determined by measuring the number of copies of the metadherin gene in the patient's cells. ...


USPTO Applicaton #: #20090324596 - Class: 4241381 (USPTO) - 12/31/09 - Class 424 
Drug, Bio-affecting And Body Treating Compositions > Immunoglobulin, Antiserum, Antibody, Or Antibody Fragment, Except Conjugate Or Complex Of The Same With Nonimmunoglobulin Material >Binds Expression Product Or Fragment Thereof Of Cancer-related Gene (e.g., Oncogene, Proto-oncogene, Etc.)

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The Patent Description & Claims data below is from USPTO Patent Application 20090324596, Methods of identifying and treating poor-prognosis cancers.

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FIELD OF THE INVENTION

The present invention relates generally to methods for identifying breast cancer patients with a poor prognosis, and to therapeutic modalities for improving prognosis by combating metastasis and abrogating chemoresistance in cancer cells.

BACKGROUND

The progression of cancer from an abnormal outgrowth to a life-threatening metastatic tumor is accompanied by a myriad of genetic and epigenetic alterations accumulated along the way. The challenge of distinguishing crucial drivers of metastasis from thousands of by-stander alterations remains a major obstacle in the battle against cancer. The turn of the century has witnessed the advent of two parallel, but individually incomplete, genomic approaches to unravel the genetics of cancer metastasis.

The first, based on comparative analyses of expression profiles of cancer cell line variants with different metastasis potentials, often obtained by in vivo selection in animal models, has led to the identification of several metastasis genes. However, much work remains to be done to validate the clinical relevance of metastasis genes identified in animal model studies.

The second approach, gene expression profiling of human tumor specimens, has enabled the identification of several poor-prognosis signatures that are predictive of recurrence and metastasis risk in human cancers. Although different poor-prognosis signatures for the same type of cancer identified in independent studies have proven to be operationally interchangeable for class prediction purposes in the clinic, the lack of gene overlap between different poor-prognosis signatures has posed a major challenge for understanding the biological underpinnings of cancer progression and metastasis, thereby hindering the development of targeted therapeutics. In other words, there is evidently no such thing as a universal “poor prognosis gene.” There is therefore a need to identify a gene signature that predicts poor prognosis across clinical classes.

SUMMARY

OF THE INVENTION

Embodiments of the present invention provide an objective means of prognostication regarding the long-term outcome of an incident of cancer. In a preferred embodiment, the invention relates to breast cancer. In other embodiments, the invention relates to immunotherapy and anti-sense therapy to combat metastasis in cancer, and to inhibit the development of cells that are resistant to chemotherapeutic agents.

In one embodiment, the invention provides a method of treating breast cancer or other cancer comprising: a) providing; i) a subject suspected of having breast cancer or other cancer, ii) an agent that inhibits an activity of metadherin, and b) administering said agent to said subject.

The method may be used when the breast cancer or other cancer is a poor prognosis cancer, including a metastatic cancer, a chemoresistant cancer, a cancer having in it a cell that has more than 2 copies of a metadherin gene, or a cancer having in it a cell that has a metadherin gene copy number greater than that of a control cell, which control cell may be a non-cancerous cell from the subject or from a reference subject, or from a breast cancer cell or other cancer cell from the reference subject.

In some embodiments, the agent may be selected from the group consisting of an antibody to metadherin, a metadherin antisense molecule, and a small molecule.

In a preferred embodiment, the inventnion provides a method for making prognosis for a subject with breast cancer or other cancer. The method comprises a) providing a cancer cell from said subject, b) determining, for said cell, a metadherin gene copy number, and c) assigning a poor prognosis to said subject if said copy number is greater than 2.

In one embodiment, the invention provides a method of reducing the development of chemoresistant cancer cells in a subject treated with a chemotherapeutic agent, the method comprising: a) administering to said subject a pharmaceutically acceptable amount of said chemotherapeutic agent, and b) administering to said subject an agent selected from the group consisting of an antibody to metadherin, a metadherin antisense molecule, and a small molecule.

In another embodiment, the invention provides a method of determining variations in the copy-number of a gene across defined populations comprising the following steps: a) calculating an expression score based on expression differences between comparison groups for each of a plurality of genes having a genomic position on a chromosome, b) ordering said expression scores based on said genomic position of each said gene, c) finding and quantifying an expression pattern for each said gene by calculating a neighborhood score for each genomic locus using a geometry-weighted sum of expression scores for all the genes on the chromosome, d) assigning a weight to each expression score based on the proximity of each gene to the locus in consideration, e) estimating the statistical significance of the neighborhood score, and f) identifying a region of potential copy number alteration.

In one embodiment, the method of determining variations in the copy-number of a gene across defined populations includes finding a stretch of 20 or more continuous aberrant neighborhood scores to detect a genomic copy number alteration.



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Cancer prognostic diagnostic and treatment methods
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stats Patent Info
Application #
US 20090324596 A1
Publish Date
12/31/2009
Document #
File Date
04/21/2014
USPTO Class
Other USPTO Classes
International Class
/
Drawings
0


Anti-
Breast
Breast Cancer
Cancer Cell
Cancers
Chemo
Gating
Immunotherapy
Measurin
Metastasis
Objective
Prognosis
Prognostic
Resistance
Sense
Stasis
Therapy


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