April 2012
Principal Investigator: Hening Lin
Co-Principal Investigator: Paraskevi Giannakakou
Co-Investigator: Robert Weiss
Department of Chemistry and Chemical Biology (Lin); Department of Pharmacology/Medicine, Weill Cornell Medical College (Giannakakou); and Department of Biomedical Sciences (Weiss)
Contact Information: Email: rsw26@cornell.edu; Phone: 607-253-4443
Sponsor: Cornell University Ithaca-Weill Cornell Medical College Seed Grants Program
Grant Number: N/A
Title: Sirt2 as A New Target for Treating Triple Negative Breast Cancer
Annual Direct Cost: $49,994
Project Period: 07/01/2012-06/30/2013
DESCRIPTION (provided by applicant): This proposal aims to develop a new treatment strategy for triple-negative breast cancers (TNBC) by a multi-disciplinary team including a chemist/biochemist, a cell biologist, and a mouse geneticist. TNBC is more difficult to treat than other types of breast cancer and there remains an over-riding need for the identification of additional targets that would lead to the development of more effective therapies. The central hypothesis of our new treatment strategy is that an enzyme, Sirt2, is essential for breast cancer cells, in particular TNBC cells, and inhibiting Sirt2 with pharmacological agents is an effective treatment for TNBC. This hypothesis arises from two exciting developments described below in the Scientific Background section. These breakthroughs have prompted us to further test this hypothesis by carrying out the following three aims:
- Test whether Sirt2 inhibitors suppress tumorigenesis in xenograft models with human TNBC cell lines or in a genetically engineered mouse model of breast cancer.
- Understand the molecular role of Sirt2 in cancer cell proliferation and determine the potential synergistic interaction of Sirt2 inhibitors with taxanes and epothilones.
- Develop more potent Sirt2 inhibitors and test their potential as anticancer agents in cell culture and mouse models of TNBC.
