An epigenetics drug currently being used to treat blood cancers and rare sarcomas may inhibit the development of bladder cancer by activating the immune system, reports a new study in mice. The drug is now being tested in a national clinical trial for patients with late-stage bladder cancer. This is the first time a drug used in hematologic malignancies and rare sarcomas has been used to treat one of the most common solid tumours.
The drug, tazemetostat, was originally developed to treat lymphoma. “We have discovered for the first time that the drug works by activating the immune system, not just by inhibiting tumors,” said lead study author Dr. Joshua Meeks, associate professor of urology and biochemistry and molecular genetics at the Northwestern University Feinberg School. Medicine and Northwestern Medicine physician/scientist. The study was published October 5 in Science Advances.
Northwestern University’s Robert H. “We think that specific mutations that can make a drug successful are found in about 70% of bladder cancers,” said Meeks, a member of the Lurie Comprehensive Cancer Center. Bladder cancer affects more than 700,000 individuals in the US
It is the sixth most common cancer overall and the fourth most common cancer in men. More than 80,000 people are diagnosed with bladder cancer each year in the US. “Survival for advanced bladder cancer is extremely poor, and the drug works by a different mechanism than any other therapy,” Meeks said. “This is the first application of epigenetic therapy in bladder cancer.” The drug is a pill that is well tolerated and can be added to other systemic therapies in bladder cancer, Meeks said.
It is being tested in a national clinical trial led by investigators at Northwestern for patients with late-stage bladder cancer. Northwest investigators showed that the drug, which targets the EZH2 gene, which is abundant in most tumors, can inhibit the development of bladder cancer.
“EZH2 is typically overexpressed in most solid tumors and works by ‘locking’ the tumor in the state of growth,” Meeks said. “We think it is one of the main genes involved in cancer. We were interested in that gene because the most common mutation in bladder cancer can make EZH2 more active. When cells have high levels of this gene activity So they grow.
“When the scientists knocked down EZH2 in bladder cancer in mice, the tumors were much smaller and filled with immune cells.” This was our clue that the immune system could be suppressed by EZH2,” Meeks said. “Next, we gave a commercially available drug. (tazemetostat) to inhibit the activity of this gene. This caused a lot of immune cells to pack the bladder.
Finally, when we used mice without T cells, we found that the drug was ineffective, confirming that the immune system was probably the primary pathway by which the drug worked. “We find that the treatment is potent immunotherapy in translational research. The drug alters the tumor to prime the immune system, activates CD4 helper cells that coordinate the immune response and recruits more T cells.” Is.”