MYC is a family of three related proteins
that are overexpressed in cancer and which contribute to an estimated 100,000
cancer deaths annually in the United States.
Efforts to block MYC directly have failed.
Fortunately, these proteins have an Achilles' heel—a chromosome-binding
cofactor called WDR5.
Understanding how MYC interacts with WDR5 and
other cofactors could lead to the development of new drugs that can effectively
block MYC and stop many cancers in their tracks.
Reporting in the Proceedings of the National
Academy of Sciences, William Tansey, Ph.D., and colleagues at Vanderbilt found
that disrupting the interaction between MYC and WDR5 in a cancerous growth
causes "rapid and comprehensive tumor regression."
"If the MYC–WDR5 connection is to be
pursued as a viable therapeutic avenue, we need to know if breaking this
connection in the context of an existing model cancer would have an impact on
tumor growth," said Tansey, co-leader of the Vanderbilt-Ingram Cancer
Center's Genome Maintenance Research Program.
That's what they did, using a
laboratory-grown model of Burkitt's lymphoma, a form of non-Hodgkin's lymphoma
or immune-cell cancer. "We now know that breaking this connection causes
these tumors to disappear," he said.
Tansey is the Ingram Professor of Cancer Research and professor of Cell & Developmental Biology and Biochemistry.
In 2015, in collaboration with Tansey's
group, a team led by Stephen Fesik, Ph.D., the Orrin H. Ingram, II Professor of
Cancer Research, solved the crystal structure of the MYC-WDR5 interaction. This
effort led to their ongoing collaboration to discover drugs that can target MYC
through WDR5.
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