Molecular Studies Provide New Clues about Rare Soft Tissue Sarcoma

Pictured: Ping Chi

Physician-scientist Ping Chi

A recent Memorial Sloan Kettering study suggests new ways to control malignant peripheral nerve sheath tumors (MPNSTs), a rare, aggressive type of soft tissue sarcoma. The primary treatment for these tumors, which form in the connective tissue around the nerves, is surgery. But when surgery is not feasible due to the location of the tumor, or because it has spread to other parts of the body, few options are available.

The investigators analyzed the genetic changes in these tumors and made discoveries that may lead to both more-accurate diagnoses and new treatments for the disease — as well as treatments for other cancers that may be driven by similar genetic changes. The study was published recently in Nature Genetics.

Looking for Biomarkers

MPNSTs are difficult to diagnose accurately because the tumors tend to be histologically diverse, meaning they can look very different from each other under the microscope. Adding to this diversity, the tumors often have complex rearrangement of their chromosomes. There are also a lack of biomarkers — molecules that can be measured in tumors to help diagnose disease.

“Therefore, our findings really surprised us,” says MSK physician-scientist Ping Chi, the study’s senior author. “We found that despite all of the clinical and histopathological differences between these tumors and the complex chromosomal rearrangements, this is actually a relatively ‘pure’ disease, with the majority of them having the same three central tumor suppressor pathways inactivated.” Tumor suppressor pathways are biochemical processes in cells that prevent tumors from forming; when inactivated, they can lead to cancer.

Potential for Targeted Therapies

Now that the investigators understand more about the genetic changes inside these tumors, they have a diagnostic biomarker that can be used for more accurate diagnosis going forward. There are also therapeutics already in clinical and preclinical development that address these particular genetic changes.

“Future therapies that focus on these pathways may benefit not only patients with MPNSTs but also other patients who have diseases associated with similar genetic changes, including pediatric glioma brain tumors and certain kinds of acute lymphocytic leukemia that preferentially inactivate one of these pathways,” says Dr. Chi, who is a medical oncologist and a researcher in the Human Oncology and Pathogenesis Program.

This research was supported by the National Institutes of Health, a Harry J. Lloyd Trust–Translational Research grant, a Charles H. Revson Senior Fellowship, Jubiläumsfonds of the Oesterreichische Nationalbank, the Sidney Kimmel Foundation, and Cycle for Survival.