For years, scientists have struggled to find a way to block a protein known to play an important role in many cancers. The protein, STAT3, acts as a transcription factor—it performs the crucial task of helping convert DNA into the RNA instructions used to make new proteins. But when overly active, STAT3 performs this task too well, fueling the growth and division of abnormal cells, and contributing to cancer. Scientists have taken various approaches to selectively blocking STAT3 in cancer, but none have produced successful treatments.
Now, researchers led by Rockefeller University's James E. Darnell, head of the Laboratory of Molecular Cell Biology, have suggested a new way to target STAT3. In research published November 9 in the Proceedings of the National Academy of Sciences, they report successfully disrupting STAT3's ability to act as a transcription factor, suggesting a basis for new, targeted approaches to fighting cancer. “We have described some interesting mutations in the STAT3 protein that, if we could mimic with a drug, could become very valuable tools in our fight against cancer,” says Darnell, Vincent Astor Professor Emeritus at Rockefeller. “Some of the mutations, in particular, seem really exciting.” Many scientists—and drug companies—have focused on STAT3 because it is overactive in virtually all of the major human cancers: breast, prostate, lung, colon, and some blood malignancies. But earlier efforts have not succeeded in finding drugs that block the protein at low enough doses, Darnell says.