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An experimental drug attacks synovial sarcoma, a rare type of tumor

Researchers at Washington University School of Medicine in St. Louis have developed a way to attack synovial sarcoma – a rare tumor of soft tissues, such as ligaments and muscles – using an experimental drug that triggers death cellular. The drug was developed by researchers at the University of Washington who are planning a Phase 1 clinical trial to study its safety and effectiveness in patients with synovial sarcoma that has spread beyond the tumor site of the drug. ‘origin.

The study is available online in the journal Clinical cancer research.

Synovial sarcoma is rare, with 900 to 1,000 new cases diagnosed each year, and is most commonly diagnosed during 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 sarcomas nationwide, as is the Siteman Kids at St. Louis Children’s Hospital.

“Synovial sarcoma is responsible for approximately 10% of all sarcomas, and because sarcoma in general is rare, many of these patients – both pediatric and adult – travel from all over the country to receive treatment at our specialized center for sarcomas,” said oncologist Brian A. Van Tine, MD, PhD, professor of medicine. “If diagnosed early, this cancer can be cured with standard care – surgery, radiotherapy and chemotherapy. But once it spreads, we no longer have effective cures, so we seek new treatment strategies that take advantage of genetic quirks. of this rare tumour. »

The researchers found that synovial sarcoma lacked an important protein that most tumors rely on to drive 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 it particularly vulnerable to inhibition of this alternative pathway. The experimental drug ACXT-3102 interferes with this alternative pathway. The interference causes volatile waste compounds called reactive oxygen species to build up inside cancer cells. When enough reactive oxygen species build up inside, the cell dies.

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“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 the sarcomas program at Siteman. “So we asked if we could use this broken defense against this cancer. When the levels of these compounds skyrocket inside the cells, they die off very quickly. »

The drug ACXT-3102 was developed by William G. Hawkins, MD, the Neidorff family and professor of surgery Robert C. Packman, and his team, to treat pancreatic cancer. Since most pancreatic cancers still have ME1, researchers will need to find a second way to attack this type of tumor. But because the metabolism of synovial sarcoma is unusual and consistent from patient to patient — the cancer-defining genetic error is present in 90-95% of all cases — researchers suspect this rare tumor could be treated with the 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 error that can be exploited, unlike other cancers that have a complex build-up many mutations whose effects are difficult to disentangle,” Van Tine said. “Because of this unique mutation, it is more difficult for synovial sarcoma cells to adapt to an attack on their energy metabolism. Finding a weakness in cancer that we can exploit based on the biology of a rare tumor is really exciting. »

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

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Source of the story:

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

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