Failure to achieve selective toxicity (or therapeutic index) and development of multidrug resistance are major problems in cancer chemotherapy. Glutathione S-transferase Pl-l isoform (GSTpi) is elevated in most cancer cells-- especially chemoresistant ones. This makes GSTpi a potential means for enhancing therapeutic index and targeting resistant tumors. We have designed several prototypes to release toxins in the presence of GSTpi. Feasibility will be demonstrated both in vitro and in vivo using tumor cells containing high GSTpi levels. Increased toxicity in elevated GSTpi versus low GSTpi controls is the expected outcome. A team of experts in GSTpi oncology/enzymology and synthetic chemistry are assembled to test this new approach. The agents could eventually lead to a much needed chemotherapeutic for treating cancer which has become resistant to commonly used cancer treatment regimens. Approximately 1/2 of the chemotherapy patients do not make it into remission due to unresponsive tumors as well as high toxicity (low therapeutic index).

Proposed Commercial Applications

The proposed research could lead to a new chemotherapeutic agent to treat both chemosensitive and chemoresistant tumors. If it is successful, such an agent is expected to have a substantial market.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
3R43CA074742-01A2S1
Application #
6054611
Study Section
Special Emphasis Panel (ZRG2 (02))
Program Officer
Forry-Schaudies, Suzanne L
Project Start
1998-09-30
Project End
2001-03-29
Budget Start
1998-09-30
Budget End
2001-03-29
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Oncopharmacia
Department
Type
DUNS #
City
Bozeman
State
MT
Country
United States
Zip Code
59715