Evaluation of DNA Methylation as a Target for Intraductal Therapy for Ductal Carcinoma in Situ of the Breast

Abstract

Ductal carcinoma in situ(DCIS), the preinvasive form of infiltrating ductal breast cancer, accounts for 20-30% of breast cancers and is treated surgically. In DCIS, the malignant cells are confined within the basement membrane, and so an ideal candidate for local therapies. Because DNA methylation is a potentially reversible mechanism for tumor suppressor gene inactivation, it is an intriguing target for molecular therapeutics. Hypothesis: DNA Methylation is altered in DCIS and is a therapeutic target for intraductal therapy. Specific Aim 1: Document the methylation status of tumor suppressor genes in DCIS. We have documented significant methylation in eight tumor suppressor genes in DCIS. Specific Aim 2: Document the feasibility of an intraductal approach to DCIS. We have successfully performed ductal lavage in 5 patients undergoing surgery for DCIS without any complications. Specific Aim 3: Identify the dose(s) of DAC with biologic activity and acceptable side effects when delivered intraductally to patients with DCIS (Phase I trial). The ultimate goal of this proposal is to evaluate DNA methylation as a target for intraductal therapy.

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Document Details

Document Type
Technical Report
Publication Date
Aug 01, 2005
Accession Number
ADA453373

Entities

People

  • Kristin A. Skinner

Organizations

  • New York University

Tags

DTIC Thesaurus Topics

  • Basements
  • Biomedical Research
  • Breast Cancer
  • Carcinoma
  • Diseases And Disorders
  • Membranes
  • Methylation
  • Neoplasms
  • New York
  • Reversible
  • Side Effects
  • Suppressors
  • Surgery
  • Therapy

Fields of Study

  • Biology
  • Medicine

Readers

  • Molecular Biology and Genetics
  • Oncology and Biomarker-Based Cancer Detection.