Evaluation of DNA Methylation as a Target for Intraductal Therapy for Ductal Carcinoma in Situ of the Breast
Annual rept. 15 Jul 2004-15 Jul 2005
NEW YORK UNIV NY SCHOOL OF MEDICINE
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Ductal carcinoma in situDCIS, 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 doses 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.
- Medicine and Medical Research