A New Weak Spot in Prostate Cancer: Disarming the Androgen Signal by Targeting PTGES3

A new study shows, published on Nature, that a little-known protein called PTGES3 helps prostate cancer cells keep using male hormone signals to grow, even when treatments are trying to shut those signals down. Blocking this helper protein cut off the cancer’s fuel supply in lab tests and slowed tumors in mice, pointing to a potential future treatment option.​

Prostate cancer often depends on the androgen receptor, a master switch that turns on growth programs when it senses male hormones like testosterone. Many modern treatments work by lowering those hormones or blocking the receptor, but cancers can learn to re-ignite this switch and keep growing.​

Researchers looked for new ways to stop this re-ignition by running a large genetic screen (CRISPR based) to find which genes are essential for the androgen receptor to function. The screen highlighted PTGES3, also known as p23, as a critical helper that cancer cells rely on to keep the androgen receptor present and active.​

When PTGES3 was turned off in several prostate cancer models that use the androgen receptor, cancer cells stopped dividing and many died, while cancer cells that do not rely on the androgen receptor were largely unaffected. In mice, dialing down PTGES3 in human prostate cancer tumors slowed growth and reduced levels of the androgen receptor inside the tumors.​

Importantly, high PTGES3 levels in patient tumor samples were linked to worse outcomes on hormone-blocking treatments. Patients whose tumors had more PTGES3 were more likely to see the cancer come back earlier and had poorer survival on first-line androgen receptor–targeted medicines, suggesting PTGES3 may be one reason some cancers resist therapy.​

This dual role makes PTGES3 a promising future target. Today’s drugs mainly block hormones or the androgen receptor itself, but PTGES3 supports the receptor from two angles: keeping it stable and helping it switch on genes. Hitting PTGES3 could therefore shut down the receptor’s signal even when the cancer has found ways around current drugs.​

While this is encouraging, it is early-stage research, and there are no approved medicines that specifically block PTGES3 yet. The findings do suggest two practical future steps: developing tests to measure PTGES3 in tumors as a marker of resistance risk, and designing drugs that safely target PTGES3 to be used alongside current hormone therapies.​

Source.