Methods of downregulating translocated oncogene expression using bromodomain inhibitors

a technology of bromodomain inhibitors and oncogenes, which is applied in the direction of instruments, peptides/protein ingredients, peptides, etc., can solve the problems of increasing the probability of relapse in many cancers, destabilizing the delicate balance of cell growth mechanisms,

Inactive Publication Date: 2019-05-09
WHITEHEAD INST FOR BIOMEDICAL RES +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

This approach effectively reduces the expression of oncogenes overexpressed due to translocation, potentially leading to tumor regression and improved treatment outcomes for aggressive malignancies by disrupting the oncogenic pathway driven by these genes.

Problems solved by technology

If the dislocated chromosome contains an oncogene, it may be removed from its usual regulatory controls and be continuously produced, thereby destabilizing the delicate balance of the mechanisms of cell growth.
Importantly, MYC overexpression correlates with lack of response to chemotherapy and increases the probability of relapse in many cancers [1].

Method used

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  • Methods of downregulating translocated oncogene expression using bromodomain inhibitors
  • Methods of downregulating translocated oncogene expression using bromodomain inhibitors
  • Methods of downregulating translocated oncogene expression using bromodomain inhibitors

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example 1

in Proteins Bind Ig Enhancers, Regulating Translocated Oncogene Expression and Function

[0132]Background and Introduction

[0133]c-Myc overexpression in cancer uncouples growth-factor stimulation and cell proliferation. c-Myc can be overexpressed through multiple mechanisms in tumor cells, including gene amplification, chromosomal translocation and single nucleotide polymorphisms (SNP). The most common mechanism is through MYC gene amplifications. This was first identified in the HL-60 human premyelocytic leukemia cell line, which contains 10 to 20 copies of the MYC gene [4, 5]. Some cancers can contain upwards of 150 copies of the MYC gene [6]. Chromosomal translocations occur in hematological malignancies, including Burkitt's lymphoma [7, 8]. The translocations typically occur between MYC and the immunoglobulin heavy chain (IgH) locus and MYC expression is then controlled by IgH regulatory elements [7-9]. Because IgH is highly expressed in B- and T-cells, this leads to massive overex...

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Abstract

Disclosed herein are novel methods and compositions useful for inhibiting interaction between a bromodomain protein and an immunoglobulin (Ig) regulatory element. The methods and compositions are particularly useful for downregulating expression of an oncogene translocated with an Ig locus, as well as for treating a cancer (e.g., hematological malignancy) characterized by increased expression of an oncogene which is translocated with an Ig locus. Also disclosed herein are methods and assays for identifying agents that interfere with binding of bromodomain proteins to Ig regulatory elements, as well as methods and assays for identifying inhibitors of bromodomain

Description

RELATED APPLICATION(S)[0001]This application is a division of U.S. application Ser. No. 14 / 342,265, filed Sep. 2, 2014, (now U.S. Pat. No. 10,071,129) which is a national stage filing of PCT Application No. PCT / US2012 / 053173, filed Aug. 30, 2012, which claims the benefit of U.S. Provisional Application No. 61 / 529,165, filed on Aug. 30, 2011. The entire teachings of the above applications are incorporated herein by reference.GOVERNMENT SUPPORT[0002]This invention was made with government support under NIH-1R01HG002668 awarded by the National Institutes of Health. The government has certain rights in the invention.BACKGROUND OF THE INVENTION[0003]Oncogenes are a group of genes which, when activated, can cause cancer. Most normal cells undergo a programmed form of death (apoptosis); activated oncogenes can cause those cells that ought to die to survive and proliferate instead. Most oncogenes require an additional step, such as mutations in another gene or exposure to environmental fact...

Claims

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Application Information

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Patent Type & AuthorityApplications(United States)
IPC IPC(8): A61K38/02A61K31/7088G01N33/50A61K31/551C07K16/00A61K31/713A61K31/7105
CPCA61K38/02A61K31/7088G01N33/5011A61K31/551C07K16/00A61K31/713A61K31/7105G01N2500/02G01N2500/10
InventorYOUNG, RICHARD A.RAHL, PETER B.BRADNER, JAMES
OwnerWHITEHEAD INST FOR BIOMEDICAL RES