A new study in mice by researchers at the Herbert Irving Comprehensive Cancer Center (HICCC) in New York has identified a promising drug combination for the treatment of muscle-invasive bladder cancer.

Rosiglitazone plus trametinib worked synergistically to not only induce tumour cell death, but also shift aggressive tumour cells to a more benign molecular subtype.

Both drugs are FDA-approved, rosiglitazone for type 2 diabetes and tremetinib for cancers including melanoma, non-small cell lung cancer, and thyroid cancer.

The research team, led by Cathy Lee Mendelsohn, is hopeful about advancing to clinical trials to evaluate the efficacy of this combination therapy in human patients.

“Despite recent advances, cystectomy is still the main treatment for patients with muscle invasive bladder cancer,” said Mendelsohn, Professor of Urological Sciences at Columbia University. “More recently, we have the approval of checkpoint inhibitors – but they only work on a percentage of tumours. We just need more avenues for treatment.”

Most bladder cancers are non-muscle-invasive and have a good prognosis. However, up to 20% can progress to muscle-invasive bladder cancer, which has a five-year overall survival rate of approximately 50%.

Mendelsohn and her colleagues used a drug combination that has shown potential for breast cancer. Studies in mice have demonstrated that rosiglitazone plus trametinib prevents both tumour growth and metastasis, turning invasive breast cancer cells into fat cells.

Rosiglitazone activates PPARG, a transcription factor that activates such trans-differentiation, and trametinib boosts PPARG signalling in the tumour.

In muscle-invasive bladder cancer, the combination therapy converted tumour cells to a more benign subtype, which may respond more favourably to certain treatments.

In mice treated with rosiglitazone plus trametinib, tumours decreased in size by an average of 91%, and in most cases, residual tumours were not detectable.

Diana Spencer, Senior Digital Content Editor, DDW