Breakthrough treatment for advanced prostate cancer could eliminate severe side effects

Researchers at Case Western Reserve University have developed a treatment for advanced prostate cancer that could eliminate a side effect so debilitating that patients often refuse the life-saving therapy.

In a study recently published in Molecular Imaging and Biology, the researchers describe how the breakthrough treatment targets prostate cancer cells as effectively as current therapies, but with dramatically reduced damage to salivary glands. The result: This treatment eliminates the severe dry mouth that makes eating, swallowing and speaking nearly impossible for many prostate cancer patients.

The treatment works by targeting PSMA (Prostate-Specific Membrane Antigen), a protein found in high concentrations on prostate cancer cells. Radioligand therapy (RTL) attaches radioactive material to a targeting molecule that acts like a GPS system, guiding the radiation directly to cancer cells while avoiding healthy tissue.

Current PSMA-targeted radioligand therapy is a precision cancer treatment that represents one of the most promising treatments for end-stage prostate cancer because it acts like a "smart bomb" that seeks out and destroys cancer cells.

The downside, however, is that this therapy often causes severe salivary gland damage, resulting in extreme dry mouth that can be so debilitating patients choose to stop treatment that might save their lives.

"Various strategies to mitigate this side effect have been attempted with limited success," said James P. Basilion, professor in the Department of Biomedical Engineering at Case Western Reserve and co-leader of the Cancer Imaging Program at the Case Comprehensive Cancer Center (Case CCC).

"Our study introduced a new PSMA-targeting ligand or molecule we call PSMA-1-DOTA with more favorable binding characteristics than existing treatments," said Xinning Wang, research associate professor in the Department of Biomedical Engineering and member of the Cancer Imaging Program at the Case CCC.

DOTA is a helper molecule that grabs onto radioactive metals and holds them tightly. This allows those metals to be connected to special targeting compounds, which can help doctors find or treat cancer more effectively.

The research demonstrated that PSMA-1-DOTA offers four times stronger binding to prostate cancer cells compared to current treatments. The treatment also significantly reduced salivary and tear gland damage, virtually eliminating the risk for dry mouth-all while offering the same tumor-fighting effectiveness of current standard radioligand therapy.

This breakthrough could fundamentally change prostate cancer care by transforming PSMA-targeted therapy from a 'last resort' option to an earlier intervention."

Zhenghong Lee, professor in the Department of Radiology and co-leader of the Cancer Imaging Program at the Case CCC

Other treatment options are typically tried before PSMA-targeted RLT because of the severe side effects. The hope is that this new treatment could allow doctors to use this approach much earlier in a patient's care.

The research included comprehensive testing on mouse models and in a human patient with metastatic prostate cancer at the Technical University of Munich in Germany. The patient study confirmed the lab findings, showing the new treatment avoided the salivary glands (potentially preventing dry mouth) while still finding and attacking prostate cancer cells.

The research team is now preparing for clinical trials late next year on about 12 prostate patients to validate the promising results and establish the most effective dosing procedures.