Therapeutic Targeting of CIMP+ Colorectal Cancers

Abstract

Widespread CpG island hypermethylation is seen in 25% of colorectal tumors and establishes a distinct subset of colorectal cancer termed CIMP. It is generally characterized by silencing of tumor suppressor genes and is associated with a poor prognosis. Recent studies implicate both repressive DNA methylation and histone modification marks at the promoter elements of these tumor suppressor genes. In line with this, we discovered a therapeutic restoration of CIMP-specific tumor suppressor CDKN2A by inhibiting DNA methyltransferases and histone deacetylases. Unfortunately, we were not able to identify other epigenetic modifiers working synergistically with DNA methyltransferases in silencing CIMP-specific tumor suppressor CDKN2A. Furthermore, overexpression of CDKN2A in CIMP-positive cells did not have any effect in disease amelioration. As we were not able to meet our proposed objectives, we have proposed changes in the direction of our project by submitting a revised SOW. These changes will be explored in detail in the Year 2 of this project.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 2018
Accession Number
AD1060235

Entities

People

  • Sylvia Mahara

Organizations

  • Monash University

Tags

DTIC Thesaurus Topics

  • Apoptosis
  • Biological Staining And Labeling
  • Biomedical Research
  • Cancer
  • Cell Line
  • Cells
  • Colon Cancer
  • Demographic Cohorts
  • Disease Attributes
  • Diseases And Disorders
  • Enzyme Inhibitors
  • Epigenetics
  • Gene Expression
  • Genetic Phenomena
  • Genetics
  • Inhibitors
  • Medical Personnel
  • Methylation
  • Neoplasms
  • Pcr Testing
  • Regulators
  • Schematic Diagrams
  • Statistical Analysis
  • Students
  • Suppressors
  • Targeting
  • Technology Transfer
  • Therapy
  • Viability

Fields of Study

  • Biology

Readers

  • Molecular and genetic basis of cancer.