Promising New Treatment Approach for Aggressive Prostate Cancer Unveiled

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Promising New Treatment Approach for Aggressive Prostate Cancer Unveiled

Promising New Treatment Approach for Aggressive Prostate Cancer Unveiled.

Researchers have illuminated the molecular mechanisms behind aggressive prostate cancer, a type of cancer that often exhibits poor responses to conventional treatment methods.

Significantly, they have identified a drug currently undergoing clinical trials that holds potential for treating this form of prostate cancer.

Adenocarcinoma or adenocarcinomatous prostate cancer is the most prevalent subtype of prostate cancer.

Promising New Treatment Approach for Aggressive Prostate Cancer Unveiled

One primary approach for treating advanced prostate cancer involves hormone therapy, aimed at inhibiting the effects of male hormones in the body to impede the growth of prostate cancer cells.

However, for some men, this treatment can lead to the cancer evolving into a more aggressive form known as Neuroendocrine Prostate Cancer (NEPC), which is highly lethal and lacks definitive treatment options.

In a recent study, researchers from the University of Michigan Medical School expanded on their previous work, identifying a pivotal driving factor behind prostate cancer cell growth and uncovering pathways that lead to the development of NEPC. Most notably, they discovered a potential treatment avenue.

The process through which adenocarcinoma transforms into NEPC is termed “lineage plasticity,” a cellular reprogramming where cells transition from one committed pathway to another as a means to circumvent treatment. The mechanisms driving lineage plasticity have not been entirely clear, but once it occurs, treatment options become extremely limited.

Lead author of the study, Joshi Alumkal, commented, “Our previous work suggested that about 15%-20% of patients, despite receiving more recent hormone therapies, saw their tumors start to grow, and these patients were losing the adenocarcinoma program and instead turning on programs, including one called neuroendocrine prostate cancer.”

Earlier research had identified that the protein Lysine-Specific Demethylase 1 (LSD1) is crucial for the survival of prostate adenocarcinoma tumors. In this current study, researchers sought to determine if LSD1 was also involved in NEPC.

Examination of tissues from metastatic prostate cancer patients revealed higher expression of LSD1 in NEPC tumors compared to adenocarcinoma tumors.

To establish LSD1’s significance, the researchers removed LSD1 from NEPC cell models and observed significantly impaired cell growth, highlighting LSD1’s essential role in the survival of these aggressive cells. Subsequent testing involved inhibiting the interaction of LSD1 with other proteins to assess its effect.

First author of the study, Anbarasu Kumaraswamy, explained, “Ultimately, we found a class of drugs that block protein-protein interaction – covalent inhibitors – to be more effective in blocking LSD1 and slowing cancer cell growth.”

With a clearer understanding of LSD1’s functioning, the researchers identified key genes and molecular pathways controlled by LSD1 in NEPC.

They found that LSD1 suppresses the TP53 gene, which provides instructions for producing the protein p53 that inhibits tumor growth. Inhibiting LSD1 in cancer cell models reactivated p53, leading to suppressed tumor growth.

“Cell lines lacking p53 are less sensitive to LSD1 inhibition, providing strong evidence that reactivation of p53 is crucial for the anti-tumor effects of LSD1 inhibition,” noted Alumkal.

The next step involved testing the efficacy of known LSD1 inhibitors. Researchers employed mouse models to test seclidemstat’s effectiveness, a drug currently in phase I clinical trials for treating sarcomas, a cancer originating in bone and connective tissue.

In each case, this drug effectively halted NEPC tumor growth and even led to complete regression in some instances.

The researchers stated that their findings offer a potential treatment avenue for NEPC and other cancer patients.

Alumkal emphasized, “The drug we’ve identified is in clinical trials, which gives us hope that we might be able to develop LSD1-targeted clinical trials for aggressive prostate cancer in the near term. These findings could also offer a more universal approach to reactivating p53 function in other cancers.”

The study was published in the journal “JCI Insight.”