New Chemical Entities With Application To Pancreatic Cancer

Larta Institute
posted on 10/10/2007

Technology Description:
UCI researchers expressed a soluble TßRII in COLO-357 human pancreatic cancer cells to determine whether blocking TGFß actions would suppress pancreatic cancer cell growth in vivo. The results showed that COLO 357 clones expressing soluble TßRII were no longer growth inhibited by exogenous TGFß1 and exhibited a marked decrease in their invasive capacity in vitro. When injected into mice, these clones exhibited attenuated growth rates and angiogenesis as compared to tumors formed by sham transfected cells. This indicates that endogenous TGFßs can confer a growth advantage in vivo to a pancreatic cancer cell line that is growth inhibited in vitro and suggest that this approach can be used to block the tumorigenic effects of TGFß.

UCLA researchers found that the simultaneous administration of plant-derived polyphenolic compounds with inhibitors of reactive oxygen species (ROS) acted synergistically to inhibit pancreatic cancer growth and tumor metastasis. In vivo studies in mice using polyphenols revealed that pancreatic cancer cells selectively underwent apoptosis while nondiseased tissue was unaffected.

Combined treatment of pancreatic cancer with TGFß and plant-derived polyphenolic compounds may down-regulate cellular survival factors while inducing apoptosis (cell death).

Technology Background:
While considerable progress has been made towards the diagnosis and treatment of a plethora of cancers, very few inroads have been made with respect to pancreatic cancer. As the 5th leading cause of cancer-related deaths in the U.S. it is amongst the most devastating with the mortality rate virtually equal to its incidence rate. Indeed, pancreatic cancer is difficult to diagnose and largely untreatable due to its highly metastatic nature.
Unfortunately current clinical protocols for the diagnosis and treatment of pancreatic cancer have been met with little, if any, success. However, human pancreatic cancers overexpress TGFßs resulting in a decreased patient survival. This resistance is addressed by treating pancreatic cancer with three transforming growth factor ß (TGFß) isoforms that regulate many cellular processes. These molecules inhibit the growth of cells of epithelial origin and modulate differentiation, migration, deposition of the extracellular matrix, immunosuppression, motility and cell death.

Advantages

• Combined therapy may reduce pancreatic tumor size and inhibit tumor metastasis.
• Polyphenol rottlerin is effective without added ROS inhibitors.
• Targeted treatment with sensitive antimicrobials.
• Potentially reduced side effects.

Innovation Details

File Number: B-102

Other Information:

Intellectual Property:
These technologies are protected by US Patent 6,953,786 and pending Applications; other rights may also pertain.

Additional Information:
Technology Bundling Project
Funded by Ewing Marion Kauffman Foundation and administered by Larta Institute, the Project’s expert panels examined technologies from 18 Southern California research centers and identified inventions which could be synergistically combined for unique solutions. These Linked-Solutions are now being offered for license, with reduced red tape and “1-stop technology shopping”

IP Protection