Method for the diagnosis, prognosis, and tratment of cancer metastasis

a cancer metastasis and prognosis technology, applied in the field of cancer metastasis diagnosis, prognosis and treatment, can solve problems such as cell change, achieve the effects of increasing the expression level of c-maf, reducing the risk of metastatic cancer, and inhibiting expression

Inactive Publication Date: 2016-02-11
FUNDACIO INST DE RECERCA BIOMEDICA (IRB BARCELONA) +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Certain chemical messengers such as hormones bind to these receptors and this results in changes in the cell.

Method used

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  • Method for the diagnosis, prognosis, and tratment of cancer metastasis
  • Method for the diagnosis, prognosis, and tratment of cancer metastasis
  • Method for the diagnosis, prognosis, and tratment of cancer metastasis

Examples

Experimental program
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Effect test

example 1

Selection of Relevant Genes

[0270]An analysis was performed, the purpose of which was to select genes that express in a differential manner in cells derived from a single ER+ breast cancer cell line in response to changes in the levels of expression of c-MAF (Table 1, FIG. 1B). The genes and functions that were determinative of the bone metastasis program mediated by c-MAF were selected following the below criteria:[0271]i) Genes the expression of which in primary tumors is significantly correlated with the expression of c-MAF.[0272]ii) Genes whose expression is modified with the expression of c-MAF, either when c-MAF is over-expressed (long or short isoform) in MCF7 cells, or when the expression of c-MAF in highly metastatic bone cells derived from MCF7 expressing c-MAF is reduced, and[0273]iii) Genes that are correlated to the expression of MAF in primary tumors and in one of the mentioned cellular conditions in ii) are considered members of the bone metastatic program mediated by ...

example 2

The Therapeutic Value and Prognostic Value of Genes Enriched for the Development of Bone Metastasis

[0275]The genes enriched in bone metastasis through the experimental system for the selection of metastatic cell populations developed here were evaluated vis-a-vis two different databases containing the expression profiles and the clinical records of 560 primary breast cancer tumors and 58 metastases from patients suffering from breast cancer. These tumors are representative of all of the sub-types of breast cancer and localizations of metastases. Both databases and the related clinical records are available to the public (GSE 2603, 2034, 12276 and 14020).

[0276]The gene expression in ER+ primary tumors of the genes taken from bone metastases demonstrated a significant correlation with a recurrence in bones and was also correlated with metastasis to bone (FIG. 1A) but not with metastasis to other tissues (FIG. 1B).

example 3

In Vivo Functional Validation of the Members of the Program for Bone Metastasis Mediated by c-MAF

PTHLH Gene

[0277]The metastatic PTHLH gene, positive during prior analysis and directly correlated with the expression of c-MAF (Table 1 and FIG. 3), was functionally validated in a metastatic colonization trial in bones in an xenograft experimental model of breast cancer metastasis in mice. The standard approximations / approaches to validate the candidate gene to direct the process of metastasis were the samples of the loss of PTHLH function in low-metastatic cells that express c-MAF. The expression of the c-MAF gene was induced in cells that were moderately metastatic in bone, in vivo, MCF7, that present low levels of expression of the gene, c-MAF. The overexpression of c-MAF was responsible for the increase in the endogenous levels of the PTHLH gene (FIG. 3). In this context the activity of the cytokine PTHLH was then blocked using an antagonist peptide (FIG. 3).

[0278]In the process for...

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Abstract

This study describes a method to determine the likelihood of the development of metastasis in a subject suffering from cancer, in addition to a method to design a customized therapy in a subject suffering from cancer, in particular breast, colon, lung, kidney and thyroid cancer, based on the determination of the expression level of one or more genes whose expression is modulated by an increase in c-MAF expression. It also describes a method for the identification of marker genes with a propensity for metastatic cancer based on inducing the modulation of the c-MAF expression Finally, the use of PTHLH and PODXL inhibitors and RERG activators in the treatment and / or prevention of the cancer, in particular breast, colon, lung, kidney and thyroid cancer.

Description

OBJECTS OF THE INVENTION[0001]This invention relates to methods to determine the likelihood a subject suffering from cancer, in particular breast, colon, lung, kidney or thyroid cancer, will develop a metastasis, in addition to methods for the creation of customized therapies for a subject suffering from cancer, in particular breast, colon, lung, kidney or thyroid cancer. Such methods consist of determining the expression level of a set of genes whose expression is related to the c-MAF gene expression. The invention also involves the use of PTHLH and PODXL inhibitors and RERG activators in the treatment and / or prevention of the metastatic cancer, in particular breast, colon, lung, kidney or thyroid cancer.BACKGROUND OF THE INVENTION[0002]Breast cancer is the second most common type of cancer worldwide (10.4%; after lung cancer) and the fifth most common cause of death by cancer (after lung cancer, stomach cancer, liver cancer and colon cancer). Is breast cancer the most common cause...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C12Q1/68C12N15/113
CPCC12Q1/6886C12N15/1135C12Q2600/158C12N2320/30C12N2310/14C12Q2600/118C12Q2600/106A61P35/00A61P35/04C07K16/32A61K38/17Y10T436/143333C12N2310/11
Inventor GOMIS, ROGERARNAL, ANNATARRAGONA, MARIAPAVLOVIC, MILICAPLANET, EVARIST
Owner FUNDACIO INST DE RECERCA BIOMEDICA (IRB BARCELONA)
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