Scientists at the University of Michigan Rogel Cancer Center have made a breakthrough in understanding how some prostate cancers transform into aggressive forms that are much harder to treat.

The team, led by Dr. Joshi Alumkal, has identified a key protein, lysine-specific demethylase 1 (LSD1), which plays a crucial role in this transformation. Their findings suggest that targeting LSD1 with specific drugs could open new doors for treating these aggressive cancers.

A Dangerous Transition

Most prostate cancers start as a type called adenocarcinomas, which are often manageable with standard treatments. However, in some cases, these tumors evolve into a far more aggressive form called neuroendocrine prostate cancer.

This process, known as lineage plasticity, leaves patients with few effective treatment options. Understanding what drives this transformation has been a long-standing challenge for researchers.

The Role of LSD1

LSD1 is a protein that regulates gene activity in both healthy and cancerous cells. Dr. Alumkal’s earlier research showed that LSD1 helps prostate adenocarcinoma cells survive by activating genes linked to stem cell-like behavior.

The new study builds on this work, revealing that LSD1 is even more active in neuroendocrine prostate tumors than in adenocarcinoma tumors.

By removing LSD1 from neuroendocrine prostate cancer cells, the researchers found they could significantly slow the cancer’s growth.

They also discovered that blocking LSD1’s interaction with other proteins, rather than its enzymatic activity, was the most effective way to stop the cancer from spreading.

A Promising Drug Candidate

One of the most exciting findings came from testing a class of drugs called allosteric inhibitors, which are designed to disrupt LSD1’s function. Among these drugs, seclidemstat showed remarkable results.

Already in phase 1 clinical trials for sarcoma, seclidemstat not only slowed tumor growth in mice but, in some cases, caused tumors to shrink completely—all without any noticeable toxicity.

Dr. Anbarasu Kumaraswamy, a key researcher on the project, highlighted seclidemstat’s potential as a game-changer for treating aggressive prostate cancers.

LSD1 and the Tumor Suppressor Gene p53

The team also uncovered another important function of LSD1: it deactivates p53, a gene known as the “guardian of the genome” for its ability to suppress tumor growth. By inhibiting LSD1, the researchers were able to reactivate p53, effectively slowing tumor progression.

This discovery suggests that reactivating p53 could be a crucial mechanism for fighting not only aggressive prostate cancer but also other types of cancer.

Hope for the Future

The implications of this research are significant. Targeting LSD1 with drugs like seclidemstat could offer a much-needed treatment option for patients with neuroendocrine prostate cancer, a condition that currently has few effective therapies.

Additionally, these findings may lead to broader applications, including the possibility of reactivating p53 in other cancers.

Because seclidemstat is already undergoing clinical trials for another cancer type, Dr. Alumkal is optimistic that clinical trials for aggressive prostate cancer could begin soon. This could speed up the process of bringing these potentially life-saving treatments to patients.

What This Means for Patients

For patients and their families, this research brings hope. Aggressive prostate cancer has been notoriously difficult to treat, but targeting LSD1 offers a new therapeutic strategy that could make a significant difference.

These findings also emphasize the importance of continued research into how cancer evolves and how to counteract these changes effectively.

As scientists explore these promising avenues, the future looks brighter for individuals battling not only prostate cancer but potentially other cancers influenced by LSD1 and p53. The study was published in JCI Insight.

If you care about prostate cancer, please read studies about 5 types of bacteria linked to aggressive prostate cancer, and new strategy to treat advanced prostate cancer.

For more information about prostate cancer, please see recent studies about new way to lower risk of prostate cancer spread, and results showing three-drug combo boosts survival in metastatic prostate cancer.

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