Reversing treatment resistance in prostate cancer: Study solves longstanding puzzle in tumor biology

Josephg

My son sent me this article, and I found it to be interesting. So, I'm sharing it.

https://medicalxpress.com/news/2025-12-reversing-treatment-resistance-prostate-cancer.html

swl1956

Great to hear a potential fix for CRPC is on the horizon. Thanks for sharing!

centralPA

The take home from the article…

Around the same time, the pharmaceutical company Novartis developed the first small molecules that could inhibit NSD2. Shen, Lu, and a growing list of collaborators synthesized one of these inhibitors and showed that in organoids made of cultured cells and in animal models, inhibiting NSD2 with the drug caused neuroendocrine prostate tumors to lose the neuroendocrine phenotype. That alone isn't enough to kill the cells, but when combined with androgen receptor inhibitors, the two drugs work synergistically, one attacking the cells and the other causing them to change lineages to respond to the attack.

Implications for reversing treatment resistance

Crucially, the study showed that this plasticity-driven treatment resistance is not a one-way street. When NSD2 was blocked, highly aggressive tumors that had already shifted into a neuroendocrine, drug-resistant state could be pushed back toward a more typical prostate cancer identity that once again relied on androgen receptor signaling. In other words, cancers that had stopped responding to hormone therapy became sensitive to it again.

This is one of the first clear demonstrations that a form of treatment resistance in prostate cancer—driven by epigenetic plasticity—can be reversed, raising the possibility that future therapies could "reset" resistant tumors rather than simply trying to work around them.

Very cool. Figuring out how to turn it into a therapy will be the key. Faster!