Most cases of gastrointestinal stromal tumor (GIST), a type of soft-tissue cancer (sarcoma), are caused by mutations in genes that can be effectively targeted with drugs that inhibit the activity of rogue cancer-promoting enzymes.
But an estimated 10% to 20% of GISTs have no identifiable or targetable mutations. Now, investigators in a Boston-area cancer research collaboration have clarified mechanisms that allow these hard-to-treat cancers to develop, and in lab experiments have identified strategies that could lead to effective new therapies.
The research, a joint effort of investigators at Dana-Farber Cancer Institute, Massachusetts General Hospital (MGH), the Broad Institute of MIT and Harvard, and the Ludwig Center at Harvard Medical School (HMS), is published in the journal Nature.
Importantly, the investigators show how “epigenetic” changes – changes in how the code of genes is read by tumor cells that are not caused by genetic mutations – can lead to the development of GISTs and other cancers, and how it may be possible to short-circuit the cancer-causing machinery.
“Your genome consists of about 6 feet of DNA wrapped very carefully to fit into microscopic cells. One of the tricks that the cell uses to compact all of this DNA is to tie it up into little loops,” says senior co-author Bradley E. Bernstein, MD, PhD, of MGH, Broad Institute and the Ludwig Center at Harvard.
