Breakthrough in treatment for advanced bladder cancer

By Margo White

Breakthrough in treatment for advanced bladder cancer
New research shows major advance in treatment for bladder cancer.

Researchers in Australia have discovered a crucial genetic marker that represents the first major advance in treatment for patients with advanced bladder cancer in 30 years.

Bladder cancer is the fourth most common cancer among men in Australia and the ninth most common cancer among women; 2800 Australians are diagnosed with the disease each year.

Researchers from the Hudson Medical Research Institute looked at why the crucial tumour suppressor gene, ATF3, disappears as the cancer progresses.

Significantly, the team also discovered that ATF3 could be reactivated with an enzyme inhibitor called pracinostat. This drug is currently in phase II clinical trials for acute myeloid leukaemia and myelofibrosis, with promising results.

The researchers also showed that once ATF3 reappeared, this resulted in reduced tumour size and an improved chance of patient survival.

Currently available treatments for advanced bladder cancer are limited to surgery and chemotherapy. For patients with recurring cancer, this usually requires increasing doses of chemotherapy which has less impact as the cancer progresses.

“We discovered that ATF3 is a vital piece of the puzzle for these patients,” Professor Williams said.

“We were able to show that pracinostat reactivates ATF3 and restores cells to their original non-tumor state and that ATF3 could potentially be used as a bio-marker for monitoring the treatment response.

“This certainly goes a long way to explaining why these patients become increasingly resistant to chemotherapy as the cancer progresses, [and that] restoring the normal functioning ATF3 gene is necessary for standard treatment to be effective,” Professor Williams said.

The team will now use pre-clinical models to confirm whether using pracinostat in combination with chemotherapy will improve patient outcomes.

The scientists believe their findings could also be used to improve treatment options for colorectal cancer, a disease in which the expression of the ATF3 gene is also lost.

The world-first finding was recently published in the journal, Molecular Cancer Therapeutics.



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