Bladder cancer discovery opens door to potential new therapeutic avenue

Researchers at the University of Queensland’s Frazer Institute have discovered the mechanism by which bladder cancer suppresses the immune system’s natural killer (NK) cells.

This discovery could allow researchers to apply existing drugs to target and neutralize the mechanism, thereby enabling NK immune cells to kill the cancer.

The TRI team led by Associate Professor Fernando Guimaraes said the research, published in the journal eBioMedicinecould lead to new therapies for bladder cancer within three to five years.

“For us, this is about unlocking the power of immunotherapy,” Guimaraes said. The team discovered that bladder cancer suppresses immune cells by releasing a protein called TGF-β, and that blocking this protein could offer a new therapy for some of the most serious types of cancer.

“Our research is a step towards clinical trials to explore the efficacy of TGF-β inhibitors combined with NK cell-based therapies,” Guimaraes adds.

Bladder cancer is the ninth most common malignancy in the world, with more than 3,000 people diagnosed in Australia and more than 1,000 deaths in 2023. It occurs when cells in the bladder wall grow and divide abnormally and uncontrollably.

The mechanism of immune suppression in bladder cancer was discovered by Guimaraes PhD candidate Joshua Wong.

“It was definitely a lightbulb moment and it’s extremely motivating to come here every day and do your best because ultimately we’re trying to find a cure for cancer,” Wong said.

Bladder cancer patient Gary Horay said the discovery gave him hope that more effective treatment options could be found. “This research is just incredible and for those of us living with bladder cancer, it’s discoveries like this that give us hope. Hope is what keeps us going,” he said.

Gary’s prognosis is good because his cancer was caught early. He was feeling unwell and had trouble urinating. So he went to the doctor and tests revealed he had cancer. “The lesson from my case is to get checked out. If you think there’s something wrong, get it checked out,” Horay said.

The standard treatment for early-stage bladder cancer is endoscopic surgery, sometimes combined with chemotherapy or immunotherapy.

In advanced disease, more invasive surgery or radiation therapy is combined with chemotherapy or immunotherapy, which are associated with significant health problems and lifelong impacts on quality of life.

Guimaraes said NK cells are components of the immune system that naturally attack cancer cells and are at the heart of new cancer treatments, including antibody-based immunotherapies. The side effects of cancer immunotherapy are generally less severe than those of chemotherapy and radiation therapy.

His team used patient samples, working in collaboration with UQ researchers and urologists at Princess Alexandra Hospital, including Dr Handoo Rhee, Professor Eric Chung and Dr Alice Nicol.