Researchers at the University of Michigan Rogel Cancer Center have uncovered a possible way to stop prostate tumors from becoming more aggressive.
Led by Dr. Joshi Alumkal, the team focused on a protein called lysine-specific demethylase 1 (LSD1), which plays a key role in how prostate tumors change and become harder to treat.
The Challenge of Aggressive Prostate Cancer
Most prostate tumors are treatable and remain as adenocarcinomas after initial treatments like surgery or radiation. However, some tumors undergo a transformation called lineage plasticity, turning into a much more dangerous form known as neuroendocrine prostate cancer.
Once this change occurs, treatment options are extremely limited, and the cancer becomes much harder to control.
The Role of LSD1 in Tumor Growth
LSD1 is a protein that controls when certain genes are turned on or off, both in normal cells and cancer cells.
In earlier research, the team showed that LSD1 is essential for the survival of adenocarcinoma prostate tumors, as it activates genes related to stem cells, which help the tumor grow and survive.
The latest findings reveal that LSD1 is even more active in aggressive neuroendocrine prostate tumors than in adenocarcinoma tumors. When the researchers removed LSD1 from neuroendocrine prostate cancer cells, the growth of the cancer slowed down significantly.
This discovery points to LSD1 as a major driver behind the progression of prostate cancer from a treatable form to a more aggressive one.
A Promising New Drug
One of the most exciting parts of the study is the discovery of a potential new drug to block LSD1. The research team found that a group of drugs known as allosteric inhibitors could stop LSD1 from working and slow down cancer growth.
Among these drugs, one called seclidemstat showed particular promise. Seclidemstat is already being tested in phase 1 clinical trials for a different type of cancer (sarcoma), but it also worked well in this study to fight aggressive prostate cancer.
In tests with mice, seclidemstat not only slowed down tumor growth but also caused some tumors to shrink completely, with no harmful side effects.
This result gives hope that seclidemstat could be an effective treatment for patients with aggressive prostate cancer in the future.
LSD1 and the Tumor Suppressor Gene p53
Another key finding of the study is how LSD1 interacts with p53, a gene that normally helps suppress tumor growth. LSD1 appears to deactivate p53, allowing cancer cells to grow unchecked.
By blocking LSD1, the researchers were able to reactivate p53, which then worked to slow down or stop tumor growth. This suggests that the effect of LSD1 inhibitors may be even more powerful when combined with the reactivation of p53.
The Road Ahead
These findings offer new hope for patients with neuroendocrine prostate cancer, a form of the disease that currently has very few treatment options.
The study suggests that drugs like seclidemstat could provide an effective new treatment strategy by targeting LSD1 and reactivating important tumor-fighting genes like p53.
Dr. Alumkal and his team are optimistic that clinical trials using LSD1 inhibitors for aggressive prostate cancer could start soon, especially since seclidemstat is already being tested in humans for other types of cancer.
This research could also lead to new treatments for other cancers where LSD1 plays a role.
In the meantime, studies continue to show the importance of lifestyle choices in reducing cancer risk. Research has found that regular exercise may help stop cancer from developing, and that vitamin D could lower the risk of dying from cancer.
Other studies suggest that eating yogurt and a high-fiber diet may reduce the risk of lung cancer. New treatments are also being developed that can reawaken the immune system to fight cancer.
This breakthrough research was published in JCI Insight and brings us one step closer to better treatments for aggressive prostate cancer and possibly other forms of cancer as well.
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