The goal of this grant application is to support the development of a mentored-career that focuses on building a foundation of mechanism-based Phase I/II therapeutic trials directed at breast cancer. It is the intent of this application to utilize currently established research relationships, which supports a mentoring environment in the design and administration of Phase I/II trials, and provides background education in the basics of scientific reason. Therapeutic trials will be designed which integrate experts in pharmacokinetic and pharmacodynamic analysis, mechanisms of apoptosis, and angiogenesis, with clinicians specializing in the treatment of breast cancer at the Ireland Cancer Center (ICC) at University Hospitals of Cleveland (UHC) and Case Western Reserve University (CWRU). With the mentoring of Dr. Scot Remick, Director of the Developmental Therapeutics Program, the investigator will test the hypothesis that the therapeutic response of breast cancer to cytotoxic treatment will be enhanced through the addition of novel therapies. Two studies will form the foundation of this hypothesis.
Specific Aim 1 : To enhance the disease-free and overall survival of patients with inflammatory breast cancer receiving doxorubicin with the addition of an angiogenesis inhibitor (SU5416). To determine if there is a correlation between disease response and changes in plasma markers of angiogenesis, tumor microvascular density, and tumor blood flow.
Specific Aim 2 : To enhance the disease response of advanced/metastatic breast cancer and other solid tumors to cisplatin and paclitaxel treatment with the addition of a retinoid, fenretinide (4HPR). To determine if there is a correlation between disease response and changes in tumor tissue retinoid receptor activation and level of apoptosis. This study will also determine if 4-HPR therapy induces in vivo expression of TIG3, a novel gene involved with apoptosis, in treated patients, and confirm that its level of expression correlates with disease response. A Phase II breast cancer trial will follow the completion of this Phase I protocol. These studies will provide a foundation for active participation of collaborative laboratories, resulting in a successful career developing a mechanism-based therapeutic research program in breast cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
1K23CA087725-01
Application #
6189773
Study Section
Subcommittee G - Education (NCI)
Program Officer
Gorelic, Lester S
Project Start
2000-09-01
Project End
2005-08-31
Budget Start
2000-09-01
Budget End
2001-08-31
Support Year
1
Fiscal Year
2000
Total Cost
$108,000
Indirect Cost
Name
Case Western Reserve University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106