Chinese researchers have launched a phase 2 clinical trial exploring whether memantine, a drug commonly prescribed for Alzheimer’s disease, could offer new hope for men with the most aggressive form of prostate cancer. The study represents a fascinating example of drug repurposing, where established medications are tested for entirely new medical applications.

The trial targets patients with metastatic castration-resistant prostate cancer (mCRPC) who have exhausted standard treatment options. This advanced form of the disease occurs when cancer cells adapt to hormone-blocking therapy, becoming resistant to conventional treatments. When these tumors undergo neuroendocrine differentiation, essentially transforming into more aggressive variants, patient survival typically drops to less than one year.

Memantine works by blocking NMDA receptors in the brain, preventing glutamate-mediated damage in Alzheimer’s patients. Recent research has revealed that these same receptors play an unexpected role in cancer progression. Studies published in prestigious journals like Cell have shown that NMDA receptors create what scientists call a “glutamatergic signaling autocrine loop” in tumors, essentially providing a communication system that fuels cancer growth and spread.

The connection between brain receptors and cancer may seem surprising, but the science is compelling. Laboratory studies have demonstrated that memantine can directly inhibit tumor cell proliferation and invasion while simultaneously enhancing the immune system’s ability to fight cancer. When combined with immunotherapy approaches, NMDA receptor antagonists eliminated most established tumors in preclinical liver cancer models.

Previous research specifically in prostate cancer has shown promising results. Turkish scientists found that memantine triggered cancer cell death through a process called apoptosis at concentrations ten times lower than metformin, another repurposed drug being studied in cancer. The Alzheimer’s medication appeared to work by disrupting key proteins involved in cell cycle progression and survival.

The current Chinese trial will test memantine in combination with standard prostate cancer treatments. The approach is methodical: patients will receive gradually increasing doses over three weeks, reaching a maintenance dose of 20mg daily, the same dose used for Alzheimer’s treatment.

Traditional cancer therapies attack the tumor itself, but this approach targets the entire tumor microenvironment, including immune cells and supporting structures that enable cancer progression.

The researchers hypothesize that by blocking NMDA receptors, memantine could prevent this deadly transformation while boosting natural anti-tumor immunity. Laboratory evidence suggests the drug promotes T-cell and natural killer cell activity while inhibiting tumor-associated macrophages that typically suppress immune responses.

The modest scale of this initial study—just 15 patients—reflects both the rarity of suitable candidates and the exploratory nature of the research. If successful, the team plans expansion to nearly 90 patients for definitive results.

The financial investment is remarkably small, with total drug costs under $300, highlighting one of drug repurposing’s key advantages: established medications with known safety profiles and affordable manufacturing costs.

Clinical trial.