Epigenetic drugs stop the growth of bladder cancer

A new study conducted in mice at Northwestern Medical School reports that an epigenetic drug currently used to treat blood cancers and rare sarcomas can stop the growth
of bladder cancer by activating the immune system.
This is the first time that drugs used for hematologic malignancies and rare sarcomas have been used to treat one of
the most common solid tumors.
The drug, called Tazemetostat, was originally used to treat lymphoma, a methyltransferase inhibitor
.

Dr.
Joshua Meeks, associate professor of urology, biochemistry and molecular genetics at Northwestern University's Feinberg School of Medicine and physician/scientist at Northwestern Medical College, said: "For the first time, we found that this drug actually works by activating the immune system, not just by suppressing tumors
.
"

The study was published in Science Advances on Oct.
5
.

"We think specific mutations have been found in nearly 70 percent of bladder cancers that may make the drug successful," said Meeks, who is also a member
of the Robert H.
Lurie Comprehensive Cancer Center at Northwestern University.

Bladder cancer, which affects more than 700,000 people in the United States, is the sixth most common cancer and the fourth most common in
men.
In the United States, more than 80,000 people are diagnosed with bladder cancer
each year.
Meeks said: "The survival rate of advanced bladder cancer is extremely low, and the mechanism of action of this drug is different
from other treatments.
" "This is the first application
of epigenetic therapy in bladder cancer.
"

Meeks said the drug is well tolerated and could be added to other systemic therapies for
bladder cancer.
Currently, researchers at Northwestern University are conducting a national clinical trial
of patients with advanced bladder cancer.

Researchers at Northwestern University found that this drug, which targets the EZH2 gene, can stop the growth
of bladder cancer.
The EZH2 gene is abundant
in most tumors.

Meeks said: "EZH2 is usually overexpressed in most solid tumors and plays a role
by 'locking' the tumor in the growth state.
We think this is one of
the main genes associated with cancer.
We are interested in this gene because the most common mutation in bladder cancer may make EZH2 more active
.
When this gene activity level is high, the cells proliferate
.
”

When the scientists removed EZH2 from bladder cancer in mice, the tumor became much smaller and filled with immune cells
.

Meeks said: "This is our clue that the immune system may be suppressed
by EZH2.
Next, we used a commercially available drug (tazemetostat) to inhibit the activity
of this gene.
It causes a large number of immune cells to fill the bladder
.
Finally, when we used mice without T cells, we found that the drug was ineffective, which confirmed that the immune system may be the main way
the drug works.
We found that this treatment is an effective immunotherapy
in translational studies.
The drug alters tumors, activates the immune system, activates CD4 helper cells, coordinates the immune response, and recruits more T cells
.
”