Researchers at the University of Michigan Rogel Cancer Center have discovered a potential mechanism behind the transformation of treatable prostate tumors into more aggressive forms.
The team, led by Joshi Alumkal, M.D., identified the protein lysine specific demethylase 1 (LSD1) as a key player in this transformation.
Importantly, they found that LSD1 inhibitors might be a promising countermeasure.
The Problem: Most prostate tumors remain as adenocarcinomas after undergoing primary treatments, but some transition into a more aggressive form called neuroendocrine prostate cancer via a process known as lineage plasticity.
Once this transition happens, very few treatment options are available.
Role of LSD1: LSD1 is responsible for turning genes on and off in both normal and cancerous cells.
The team’s prior work indicated that LSD1 is crucial for the survival of prostate adenocarcinoma tumors by activating genes linked to stem cells.
Recent Findings: The team found that LSD1 is more active in neuroendocrine prostate tumors than in adenocarcinoma ones.
By removing LSD1 from neuroendocrine prostate cancer cells, the cancer’s growth was significantly hindered.
They determined that blocking LSD1’s interaction with other proteins was more effective than halting its enzymatic function.
New Drug Potential: Anbarasu Kumaraswamy, Ph.D., highlighted the effectiveness of a class of drugs called allosteric inhibitors in inhibiting LSD1 and curtailing the growth of cancer cells.
Among the drugs tested, seclidemstat, already in phase 1 clinical trials for sarcoma, showed great promise by not only inhibiting tumor growth but also regressing some completely, all without any observable toxicity in mice.
LSD1’s Influence on p53: The team also discovered that LSD1 deactivates p53, a critical tumor suppressor gene.
Inhibiting LSD1 reactivated p53, resulting in suppressed tumor growth, suggesting the importance of p53 reactivation in the potential anti-tumor effects of LSD1 inhibition.
Implications
This research implies that targeting LSD1 with inhibitors, such as seclidemstat, may offer a new therapeutic avenue for patients with neuroendocrine prostate cancer.
Additionally, these findings may pave the way for reactivating the p53 function in other cancers, offering a broader potential therapeutic strategy.
Given that seclidemstat is already in clinical trials, Alumkal is optimistic about the rapid development of clinical trials targeting LSD1 for aggressive prostate cancers and its potential generalizability in treating other cancers.
If you care about cancer risk, please read studies that exercise may stop cancer in its tracks, and vitamin D can cut cancer death risk.
For more information about cancer, please see recent studies that yogurt and high-fiber diet may cut lung cancer risk, and results showing that new cancer treatment may reawaken the immune system.
The study was published in JCI Insight.
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