Scientists have successfully disrupted the function of a cancer gene involved in the formation of most human tumours by tampering with the gene's "on" switch and growth signals.
The results, achieved in multiple myeloma cells, offer a promising strategy for treating not only myeloma but also many other cancer types driven by the gene MYC, according to the study authors.
"Cancer is a disease of disregulation of growth genes in a cell, and MYC is a master regulator of these genes," said James E. Bradner, MD, of Dana-Farber Cancer Institute, one of the study's senior authors.
Previous attempts to shut down MYC by inhibiting it directly with drug molecules have been notably unsuccessful.
"In this study, our idea was to switch MYC off, interfering with its ability to activate the cell-growth program," Bradner explained.
They did so with a small molecule called JQ1, developed by Dana-Farber's Jun Qi, PhD, and a co-author of the new study.
In myeloma, the immunoglobulin enhancers act on the out-of-place MYC gene like an impatient finger at a doorbell, repeatedly activating it.
Researchers found that the enhancers are loaded with a "bromodomain" protein called BRD4, which, they demonstrate, is used to switch on MYC.
When investigators added JQ1 to laboratory samples of myeloma cells, the bromodomain proteins fell off the enhancers and the enhancers abruptly stopped working. The result: a shutdown of MYC and a slowdown of cancer cell division.
"In a sense, the JQ1 molecule cuts the cable that activates MYC and also connects MYC to the cell-growth genes. The signal is interrupted and growth abruptly stops," Bradner said.
Their findings are being published by the journal Cell on its website Sept. 1 and in its Sept. 16 print edition.