Expert in sarcoma at the Memorial Sloan Kettering Cancer Center, Dr. Ping Chi, gave a presentation as part of the Cancer Biology Seminar Series at the University of Wisconsin Nov. 13. The seminars are hosted by the McArdle Laboratory for Cancer Research and are ongoing at UW.

Chi’s research examines how understanding DNA during the cell life cycle influences cancer development and how this knowledge can be applied to cancer treatment.

Chi’s presentation focused on malignant peripheral nerve sheath tumors, a type of cancer that forms in the cells that cover nerves in the peripheral nervous system. MPNST falls under a class of cancers called sarcomas, which are cancers of soft tissues in the body, Chi said.

MPNST is an aggressive cancer that largely occurs in adolescents. Chi said that about 50% of tumors are neurofibromatosis type 1 tumors. NF1 is a genetic condition where a mutation occurs in the gene and leads to tumors growing in nerve tissues around the body. The condition is often benign, but around 16% of NF1 patients will get MPNST during their lifetime, according to Dr. Chi.

Benign tumors may become cancerous after PRC2, a DNA methylation complex, stops functioning, Chi said. PRC2 regulates DNA transcription, the process by which proteins are created in the cell. Once PRC2 stops working properly, the cell stops being able to signal that it is cancerous to the body. This provides further complication with treatment, as other drugs that work with the immune system to kill cancer cells don’t work effectively to treat MPNST with disabled PRC2.

Chi’s lab examined other ways to attack MPNST cancers based on the deregulation of DNA, Chi said. They looked at the effect of DNMT1 inhibitors, which inhibit a protein that also works with DNA methylation. Chi’s lab saw that tumors without PRC2 stopped growing after treated with DNMT1 inhibitors.

Chi believed this is caused by a pathway where molecules similar to viral genetic material are created. The cell then activates pathways which lead to apoptosis, or self-mediated cell death.

This type of treatment is used in some cancers but it struggles with eliminating tumors. Chi’s lab is continuing to see if this treatment will be a viable option to cure MPNST cancers.

“We need to push [DMNT1 inhibitors] further to induce cell death, to where we could have a true therapeutic window,” Chi said.