In the quest to combat prostate cancer, researchers from the University of Michigan Rogel Cancer Center have made a significant discovery.
The team, led by Dr. Joshi Alumkal, has uncovered a key factor that could turn the tide against aggressive forms of prostate cancer.
They’ve identified a protein, known as lysine specific demethylase 1 (LSD1), which plays a pivotal role in the transformation of manageable prostate tumors into more daunting, aggressive types.
The study focuses on a critical issue: while most prostate tumors remain treatable after initial treatments, a fraction morphs into a more formidable variant known as neuroendocrine prostate cancer.
This transformation, driven by a process termed lineage plasticity, leaves patients with scant treatment options.
LSD1 is not just any protein; it acts as a genetic switch in both healthy and cancerous cells, turning genes on or off.
Previous investigations by Alumkal’s team revealed LSD1’s essential role in keeping prostate adenocarcinoma tumors alive, by activating stem cell-associated genes.
Their latest findings take this a step further, showing that LSD1 is even more active in neuroendocrine prostate cancer than in adenocarcinoma.
The team experimented by removing LSD1 from neuroendocrine prostate cancer cells and observed a significant reduction in the cancer’s growth.
They discovered that blocking LSD1’s ability to interact with other proteins was a more effective strategy than merely stopping its enzyme function.
Here’s where the story gets even more promising: Dr. Anbarasu Kumaraswamy and the team tested drugs known as allosteric inhibitors against LSD1.
Among these, seclidemstat stood out. Already in phase 1 clinical trials for treating sarcoma, seclidemstat not only halted the growth of prostate cancer cells but, in some cases, even reversed it completely—without harming the mice used in the study.
Another breakthrough involved LSD1’s effect on p53, a gene crucial in suppressing tumors. The team found that LSD1 deactivates p53. Inhibiting LSD1, therefore, reactivates p53, leading to the suppression of tumor growth.
This insight opens up new avenues for treating not just prostate cancer but potentially other cancers by reactivating p53.
The implications of this research are vast. Targeting LSD1 with inhibitors like seclidemstat offers a new hope for treating neuroendocrine prostate cancer, a variant notoriously difficult to manage.
Moreover, the potential to reactivate p53 suggests a broader applicability in cancer treatment.
Dr. Alumkal is optimistic about the rapid progression toward clinical trials targeting LSD1 for aggressive prostate cancers, buoyed by the fact that seclidemstat is already undergoing clinical evaluation.
This optimism extends to the potential for using LSD1 inhibitors in a wider array of cancers, heralding a new direction in cancer therapy.
The journey to conquer cancer is long and fraught with challenges, but discoveries like these light the path forward, offering new strategies to fight back against this formidable disease.
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