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hsp90 Decoy Peptides for Treatment of Tumors

MCW #1492

 

 Key Inventor

Kirkwood Pritchard, PhD

 State-of-the-Art

Tumors are treated by surgery, radiation, chemotherapy and/or biotherapy dependent on their type and location. The only FDA approved biotherapeutic to date is Bevacizumab (anti-vascular endothelial growth factor) that inhibits blood flow to a tumor so it "starves". Bevacizumab is more effective in some cases in a treatment cocktail with the biotherapeutic erlotinib (anti-epidermal growth factor receptor). However, bevacizumab is most commonly used with a chemotherapeutic agent such as irinotecan.

 Problem  

Bevacizumab, especially in combination with a chemotherapeutic, has a number of potentially serious side effects including hemorrhage, hypertensive crises, congestive heart failure, and nephrotic syndrome. The most common adverse events of any severity among the 742 patients receiving AVASTIN in Genentech-sponsored studies were pain, abdominal pain, headache, hypertension, diarrhea, nausea, vomiting, anorexia, constipation, upper respiratory infection, and proteinuria.

Tumor treatment varies dependent on the tissue and cancer type. Any treatment that can increase efficacy while decreasing side-effects is valuable to the patient and holds promise for significant revenue.   

 Solution

The association of heat shock protein 90 (hsp90) with endothelial nitric oxide synthase (eNOS) plays an important role in the generation of nitric oxide (•NO). Inhibition of hsp chaperone activity not only decreases •NO production but also increases eNOS-dependent superoxide anion (O2ˉ) production. Drs Xu, Shi and Pritchard have co-developed hsp90 decoy peptides that disrupt hsp90 association with eNOS. Disruption of hsp90 association with eNOS inhibits eNOS-dependent •NO generation and vasodilatation by a mechanism that changes eNOS function from an •NO synthase into a O2ˉ generating NADPH oxygenase. As •NO plays an important role in tumor angiogenesis these peptides have been shown to be highly effective inhibitors of tumor angiogenesis and demonstrated a 75% reduction in tumor growth when tested on mouse models.  

 Benefit 
  • Targets cancer progression associated with free-radical
  • Demonstrates significant tumor size reduction in mouse model system
  • Potential treatment of other vascular-disease states such as hypotension, septic shock and pulmonary edema
  • Therapeutic compound is simple peptide
 Stage of Development 

This technology has been tested through in vitro and in vivo mouse tumor models.

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MEDICAL COLLEGE OF WISCONSIN
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Summary Information

Patent Status:
11/505,036  

Mechanism of Action:
Antagonist

Molecule Type:
Peptide
Biologic

Patent Coverage Type:
Composition of Matter
Method of Use

Geographical Coverage:
US Patent

Related Areas of Interest:
Cancer

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