New Prostate Cancer Treatment Tackles the Side Effect That Makes Patients Quit

Researchers at Case Western Reserve University have developed a breakthrough prostate cancer treatment that could solve one of the field's most heartbreaking problems: patients who refuse life-saving therapy because the side effects are too severe to bear. The new treatment targets cancer cells four times more effectively than current options while virtually eliminating the debilitating dry mouth that makes eating, swallowing, and speaking nearly impossible.

How Does This New Treatment Work?

The treatment uses a precision approach called radioligand therapy (RLT), which works like a GPS-guided missile system for cancer cells. It targets Prostate-Specific Membrane Antigen (PSMA), a protein found in high concentrations on prostate cancer cells. The therapy attaches radioactive material to a targeting molecule that guides radiation directly to cancer cells while avoiding healthy tissue.

The key innovation lies in a new targeting molecule called PSMA-1-DOTA, which has more favorable binding characteristics than existing treatments. DOTA acts as a helper molecule that grabs onto radioactive metals and holds them tightly, allowing those metals to be connected to special targeting compounds that help doctors find or treat cancer more effectively.

What Makes This Treatment Different From Current Options?

Current PSMA-targeted radioligand therapy represents one of the most promising treatments for end-stage prostate cancer, acting like a "smart bomb" that seeks out and destroys cancer cells. However, this therapy often causes severe salivary gland damage, resulting in extreme dry mouth so debilitating that patients choose to stop treatment that might save their lives.

The research demonstrated several key advantages of the new PSMA-1-DOTA treatment:

• Binding Strength: Offers four times stronger binding to prostate cancer cells compared to current treatments
• Reduced Side Effects: Significantly reduced salivary and tear gland damage, virtually eliminating the risk for dry mouth
• Equal Effectiveness: Maintains the same tumor-fighting effectiveness as current standard radioligand therapy

"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.

Could This Change When Patients Receive Treatment?

This breakthrough could fundamentally transform prostate cancer care by changing PSMA-targeted therapy from a "last resort" option to an earlier intervention. Currently, 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.

"This breakthrough could fundamentally change prostate cancer care by transforming PSMA-targeted therapy from a 'last resort' option to an earlier intervention," said Zhenghong Lee, professor in the Department of Radiology and co-leader of the Cancer Imaging Program at the Case Comprehensive Cancer Center.

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 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.