Discovery of New Small Molecule Strategies to Target Cancer-Causing Proteins
2017 Harrington Scholar-Innovator
CD437 was identified as a cancer-specific toxin nearly 20 years ago. CD437 causes complete cell death of cancer but not normal cells. In spite of its promise, CD437 has not been advanced into clinical trials because its protein target remained unknown.
The Nijhawan lab discovered that CD437 acts by binding to the enzyme DNA polymerase alpha (POLA1). POLA1 is required for DNA replication, and inhibition of POLA1 in cancers cells leads to cell death. With knowledge of the CD437 target, the Nijhawan lab, with support from Harrington Discovery Institute, is poised to optimize its structure and action.
Dr. Nijhawan is seeking expertise and guidance from the Harrington Discovery Institute’s Innovation Support Center experts on the design of a POLA1 inhibitor as a first-in-class drug.
“Every patient I see dies. Most of my patients have few treatment options, and in many cases, they are getting the same medications that their parents would have received. We are trying to find new ways to target cancer-causing proteins to develop new treatments and discover something different.”
“Finding the protein target of a cancer toxin is an incredibly interesting problem. A compound causes cells to die by targeting one of nearly 20,000 proteins. Which one is it? We enjoy the hunt.”
“I am very much a physician-scientist, but I am a pure scientist as well. There are hundreds of small molecules that kill cancer. We take these molecules and try to discover their protein targets in the cell.”