Members of the Program develop and test anti-cancer treatments through the synthesis of new chemical entities and through pre-clinical mechanism of action studies of chemical and immunological agents on targets and pathways causally linked to cancer. The development of valid correlative assays or biomarkers with which to evaluate molecular responses to the agents and/or select patients for specific therapies is an important goal for the future of cancer treatment.

The strength of the Program in new compound development and clinical testing can be illustrated by the three large NCI multi-investigator grants: U19 CA113297 “National Cooperative Drug Discovery Group for Cancer” (Shen, PI), U01 CA062491 “Early Clinical Trials of New Anti-Cancer Agents” (Wilding, PI) and U10 CA021076 “Eastern Cooperative Oncology Group-Wisconsin Studies” (Stewart, PI). Very few, if any, other cancer centers have that diverse scope, from chemical synthesis/discovery, to first in human testing, to definitive Phase II and III clinical studies, of multiinvestigator drug development grants.

Program Profile

Membership:
54 members
23 departments
   6 schools

Project Funding as of 9/2006 (direct costs):

Peer-reviewed	$12.8M	82
NCI	$5.9M	36
NIH	$4.3M	26
ACS	$0.4M	3
NSF	$1.1M	9
Other P-R	$1.1M	8
Non peer-reviewed	$3.3M	68
Total	$16.1M	150

Members in the Experimental Therapeutics Program, working together with colleagues in the other six UW Carbone Cancer Center (UWCCC) Programs and the UWCCC Disease Oriented Working Groups (DOWGs), seek to identify new chemical and immunological agents for the treatment of cancer, test these agents in human clinical trials, and identify valid correlative assays or biomarkers with which to evaluate molecular responses to the agents.

The Specific Aims of the Experimental Therapeutics Program are:

1. To identify or synthesize new natural products or synthetic compounds that have anti-cancer activity or improve anti-cancer drug delivery.
2. To characterize the mode of action of chemical and immunological agents on cancer targets and pathways using assays in cancer cells and animal models and to advance promising new agents from the laboratory to Phase I clinical trials.
3. To test the safety and efficacy of new chemical and immunological agents in Phase I clinical trials and to evaluate biomarkers and correlative assays for drug activity.
4. To advance promising new therapies from Phase I into Phase II and Phase III clinical trials.

Significant Recent Discoveries

• Elucidation of the gene cluster responsible for enediyne biosynthesis. (Science 297:1173-6, 2002, and Science 297:1170-3, 2002)
• Enhanced anticancer activity of glycosides via neoglycorandomization. (Proc Natl Acad Sci USA 102:12305-10, 2005)
• Development of inhibitors of specific protein-protein interactions through the use of foldamers and peptoids. (J Am Chem Soc 127:11966, 2005 and Org Lett 7:1521-4, 2005)
• Development and clinical testing of a DNA vaccine encoding prostate acid phosphatase. (Vaccine 24:293- 303, 2006)
• Selective inhibition of TGF-ß responsive genes through the use of peptide aptamers. (Oncogene 24:3864- 74, 2005)
• Demonstration of antiandrogen activity of the antioxidant moiety of vitamin E. (Mol Cancer Therapy 4:910- 7, 2003)
• Clinical testing of new antiangiogenesis agents. (JCO 21:223-31, 2003; JCO 23:5464-73, 2005).
• Development of raf-1 activators and glycogen synthese kinase 3-beta inhibitors for the treatment of neuroendocrine tumors (patents pending).
• Comparison of four regimens for the treatment of advanced lung cancer. (NEJM 346:92-8, 2002)

Recent Experimental Therapeutics Publications