Two Yale chemists have been awarded $2.5 million from the National Cancer Institute to investigate novel approaches to treating cancers previously thought “undruggable.”
Professors Alanna Schepartz and Andy Phillips will focus on developing molecules that can enter cells and activate or inhibit genes dependent on the protein p53, often called the “guardian of the genome” for its important role in preventing cells from becoming cancerous.
Schepartz, the Milton Harris ’29 Ph.D. Professor of Chemistry and director of the Yale Chemical Biology Institute at the West Campus, said much of the research related would take place at West Campus.
The research team also includes Professor Dylan Taatjes of the University of Colorado.
Said Phillips, professor of chemistry, “I’m excited about this special opportunity to engage two great colleagues on a spectrum of science that we all share a passion for — the interplay between ‘undruggable’ targets in cancer biology and the development of new paradigms in chemical biology.”
The highly competitive grant, to be distributed over five years at about $500,000 annually, comes through NCI’s “Provocative Questions” program. It challenges researchers to focus on important but neglected problems. It also requires researchers to select a specific question to address from a list prepared by NCI.
The Schepartz-Phillips team picked question 18: “Are there new technologies to inhibit traditionally ‘undruggable’ target molecules, such as transcription factors, that are required for the oncogenic phenotype?”
“Transcriptional deregulation is one of the key features of cancer, and there are many potential points of intervention,” Phillips said. “A longstanding goal has been to directly modulate erroneous transcription factor function, and an increasing number of genomic characterizations of cancers have underscored the value and impact that such capabilities might have for patients. We had all been thinking about ways to have an impact on this seemingly obvious problem that many others view as impossible. This was a perfect opportunity for us to coordinate our thoughts and address the challenge of ‘drugging one of the poster child transcription factors in cancers: p53.”
The Yale Chemical Biology Institute at West Campus promotes innovation at the intersection of chemistry, biology, engineering, physics, and medicine.