Experimental Drug Targets Synovial Sarcoma, a Rare Type of Tumor – Genetics News

Researchers at Washington University School of Medicine in St. Louis have developed a method to attack synovial sarcoma – a rare tumor of soft tissues such as ligaments and muscles – with an experimental drug that induces cell death. The drug was developed by University of Washington researchers who are planning a Phase 1 clinical trial to evaluate its safety and effectiveness in patients with synovial sarcoma that has spread beyond the drug’s tumor site.

The study is available online in the journal Clinical Cancer Research.

Synovial sarcoma is rare, with 900 to 1,000 newly diagnosed cases per year, and is most commonly diagnosed in adolescence and early adulthood. The Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine is a major center for the treatment of sarcoma nationwide, as is Siteman Kids at St. Louis Children’s Hospital.

“Synovial sarcoma accounts for approximately 10% of all sarcomas, and because sarcomas are generally rare, many of these patients – both children and adults – travel from across the country to be treated at our specialist sarcoma center,” said oncologist Brian A. Van Tine, MD, PhD, professor of medicine. “If diagnosed early, this cancer can be cured with standard treatments – surgery, radiation therapy and chemotherapy. But once it spreads, we don’t have any effective cures, so we’re looking for new treatment strategies that take advantage of genetic peculiarities. this rare tumor. »

The researchers found that synovial sarcoma lacks an important protein that most tumors depend on to fuel their energy metabolism. The lack of this key protein – called malic enzyme 1 (ME1) – forces synovial sarcoma tumors to rely on a different metabolic pathway, making them particularly vulnerable to the inhibition of this alternative pathway. The experimental drug ACXT-3102 disrupts this alternative pathway. The interference causes volatile waste compounds called reactive oxygen species to accumulate in cancer cells. If enough reactive oxygen species build up inside, the cell dies.

“Because they lack ME1, these tumor cells are already crippled in their ability to fight damage from reactive oxygen species,” said Van Tine, who leads Siteman’s sarcoma program. “So we asked if we could use these broken defenses against this cancer. When the levels of these compounds in cells skyrocket, they die off very quickly. »

The drug ACXT-3102 was developed by William G. Hawkins, MD, the Neidorff family and surgery professor Robert C. Packman and his team to treat pancreatic cancer. Since most pancreatic cancers still have ME1, researchers need to find a second way to target this type of tumor. However, since the metabolism of synovial sarcoma is unusual and consistent from patient to patient – the cancer-defining genetic defect is present in 90-95% of all cases – the researchers suspect that this rare tumor could be treated with ACXT-3102 alone.

“Synovial sarcoma is caused by a very specific genetic mutation, so it’s a relatively clean cancer, meaning it has a single specific genetic flaw that can be exploited, unlike other cancers, which have a complex makeup of many mutations, the implications of which are difficult to disentangle,” said Van Tine. “Because of this unique mutation, it is more difficult for synovial sarcoma cells to adapt to an attack on their energy metabolism. It’s really exciting to find a weakness in cancer that we can exploit based on the biology of a rare tumor. »

The drug ACXT-3102 was licensed to a University of Washington start-up called Accuronix Therapeutics, co-founded by Hawkins to develop new cancer therapies.

Source of the story:

Materials provided by Washington University School of Medicine. Originally written by Julia Evangelou Strait. Note: Content can be edited for style and length.

#Experimental #Drug #Targets #Synovial #Sarcoma #Rare #Type #Tumor #Genetics #News

Leave a Comment

Your email address will not be published.