Methods for identification of compounds capable of selectively eliminating cancer cells with specific loss-of-function alterations

Description:

Summary of the Invention

Researchers at TGen have patented a method for identifying molecules that reduce viability of cancer cells with a specific pattern of a loss-of-function genetic alteration. These molecules are identified by creating a matched pair of isogenic cell lines that differ only by a siRNA "knock down" of a single DPC4 gene. The matched pair of isogenic cell lines are then screened against a molecular library to identify any molecules that diminish cell survival in the DPC4 deficient cell line relative to the control. The differential effect in cell survival is then confirmed in either an in vivo or in vitro tumor model. This patent also includes several novel compounds that have already been identified using this method, along with their production methods and therapeutic uses.

 

Background Information

Existing genetically selective antitumor agents predominantly target cancer cells with gain-of function alterations. However, this technology is based upon the discovery of certain families of compounds that selectively target cancer cells exhibiting a particular loss-of-function alteration, which represents a significant innovation.

 

Potential Applications

This screening method can identify compounds capable of selectively eliminating cancer cells with specific loss-of-function alterations including mutations, deletions, hypermethylations, and other types of gene silencing. Specific small molecules that selectively kill DPC4 deficient pancreatic cancer cells have already been identified.

 

Link to Issued US Patent 8,394,742

Patent Information:
Category(s):
Therapeutics
For Information, Contact:
Katie Bray
Intellectual Property Counsel
The Translational Genomics Research Institute
kbray@tgen.org
Inventors:
Haiyong Han
Daniel Von Hoff
Hong Wang
Gary Flynn
Keywords: