Breakthrough heralds hope for advanced bladder cancer patients

Researchers at Hudson Institute of Medical Research have discovered a crucial genetic marker that heralds better treatment and outcomes for patients with advanced bladder cancer.

Professor Bryan Williams and Dr Dhanya Sooraj have discovered a crucial genetic marker that heralds better treatment and outcomes for patients with advanced bladder cancer.
Professor Bryan Williams and Dr Dhanya Sooraj

The world-first finding recently published in the prestigious journal, Molecular Cancer Therapeutics may represent the first major progress in treatment for advanced bladder cancer patients in thirty years.

Each year more than 2800 Australians are diagnosed with bladder cancer. It is the fourth most common cancer among men and the ninth most common cancer among women. Because of high recurrence rates and continuing invasive monitoring bladder cancer also has the highest lifetime treatment costs per patient of all cancers.

Currently available treatments for advanced bladder cancer are limited to surgery and chemotherapy which, for recurrent patients, requires larger doses and has less impact as the cancer progresses.

Solving the puzzle

Hudson Institute researchers Dr Dhanya Sooraj, Professor Bryan Williams, Dr Dakang Xu, and Dr Jason Cain investigated why the crucial tumour suppressor gene, ATF3, disappears as the cancer progresses and is correlated with poor survival rates.

Significantly, the team discovered that ATF3 could be reactivated in bladder cancer cells using a drug currently in cancer clinical trials, called pracinostat (an enzyme inhibitor), and that once ATF3 reappeared this resulted in reduced tumour size and an improved chance of survival.

“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, restoring the normal functioning ATF3 gene is necessary for standard treatment to be effective,” Professor Williams said.

“The results shows that repairing ATF3 has the potential to be an effective new treatment approach for the majority of these patients when used in combination with chemotherapy.

“Pracinostat could potentially be used to increase a positive response to chemotherapy, by reducing the dose of chemotherapy needed and ultimately improving survival and quality of life.”

Next steps

The team will now use pre-clinical models to confirm whether using pracinostat in combination with chemotherapy can improve treatment outcomes. Pracinostat is already in phase II clinical trials for acute myeloid leukaemia and myelofibrosis, with promising results.

“We hope to show that giving a patient pracinostat prior to chemotherapy can restore ATF3, allowing for more effective and efficient chemotherapy to reduce tumour burden and ultimately increase the response to standard treatments and improve survival,” Professor Williams said.

“We also want to test pracinostat in combination with emerging treatments for bladder cancer which stimulate the immune system to help clear tumours. This new area is showing hope for patients where chemotherapy has failed,” he said.

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

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