UPDATE: Memantine for Neuroendocrine Prostate Cancer, Early Efficacy Signals

Prostate cancer can become harder to treat when it changes from the usual adenocarcinoma form into neuroendocrine prostate cancer, or NEPC. A recent study suggests that this transition may begin earlier than expected, during an intermediate phase when the cells are still partly prostate-like but are already starting to acquire neuroendocrine features.

A central finding is the role of HOXD11, a transcription factor that appears to help start this shift. In the models studied, HOXD11 was activated early and then turned on genes linked to neuroendocrine behavior, including pathways involving NMDAR signaling. When HOXD11 was suppressed, the cancer cells kept more of their normal prostate characteristics and showed less neuroendocrine change.

The work also looked at memantine, a drug known from other medical uses, as a way to block this pathway (we talked about it in this article). In preclinical models, memantine slowed the progression toward NEPC and reduced the neuroendocrine program. There was also an early clinical signal in a patient with advanced NEPC, where treatment was associated with radiographic regression, but that is still very limited evidence.

The point of the clinical trial is that memantine may help interrupt the biological switch that allows prostate cancer to become treatment-resistant and evolve into NEPC.

Source.