Unmet Need: One of the hallmarks of cancer cells is metabolic reprogramming for faster metabolism and cell growth. For example, increased glycolysis has long been known to be part of cancer cells’ biochemical adaptation. One of the key enzymes of glycolysis is glyceraldehyde-3-phosphate dehydrogenase (GAPDH) which catalyzes the first step of energy rich/ redox molecule producing reaction. There is a great need in the art to identify potential therapeutic strategies and compositions that target energy metabolism in the treatment of cancer.
The present invention provides a method for inhibiting or treating cancer with a therapeutically effective amount of mutant Glyceraldehyde-3-phosphate Dehydrogenase (GAPDH) expressed using a tumor-specific promoter thereby avoiding toxicity in healthy tissue.
Technology Overview: JHU inventors have found that mutant GAPDH inhibits the activity of wild type GAPDH and can affect cancer cell viability. JHU inventors have determined the nucleic acid sequence in expression vectors encoding mutant GAPDH proteins useful for making recombinant mutant GAPDH. Dominant negative expression is controlled by a tumor-specific promoter hence minimizing toxicity or unwanted side effects. JHU is seeking partners to develop the mutant GAPDH into pharmaceutical compositions to treat cancers.
Stage of Development: Proof of concept in human cells, and animal models demonstrating that mutant GAPDH promotes antitumor effects