Metformin and Prostate Cancer: Promising Research and Potential Benefits

2023-11-08 13:59:00

In the years in which the study was conducted in 2005, it was found that diabetic patients who took metformin had lower rates of cancer. Oncologists were excited at the prospect of using an inexpensive, safe, and widely used diabetes drug to prevent or slow the development of many types of cancer.

But in studies of prostate cancer, metformin’s performance has been mixed, with some studies indicating a lower incidence of prostate cancer among men who use metformin and other studies finding no relationship.

A study published in the journal European Urology by researchers from Colombia indicated that metformin is indeed a promising drug, and can prevent the development of prostate cancer for tumors with low levels of the NKX3.1 protein, which are more likely to develop into aggressive cancers.

“The new work reinvigorates the idea of ​​using this safe, inexpensive drug in a way that could “It will benefit prostate cancer patients, potentially spare them from additional treatment, and allow us to test the drug in a more focused way.”

The researchers found that metformin restores cancer-fighting mitochondrial activity, which is lost when NKX3.1 protein levels are low, prevents the development of prostate cancer in mice, and is associated with improved survival in patients with low-grade tumors.

“We see that metformin has the greatest effect on patients who have just been diagnosed with prostate cancer,” explains Alex Papachristodoulou (associate research scientist), who conducted the research in the laboratory of Corey Abate Shin.

“Metformin can be given to monitored patients with high-risk tumors when there is time to prevent the disease from progressing to an advanced stage,” he says.

Mitochondrial connection

The idea of ​​testing metformin and its interaction with the protein NKX3.1 evolved from previous studies, and low levels of the protein NKX3.1 have been linked to aggressive disease for years. But it was not clear what caused the decrease in cancer development.

Papachristodoulou and Abate Shen found that when prostate cells are exposed to oxidative stress (as occurs during the development of prostate cancer), the NKX3.1 portin moves to the cells’ mitochondria to reduce stress and protect the cells. If NKX3.1 levels are low, there is less protection, and prostate cells are more likely to turn malignant.

In mice and men, metformin slows prostate cancer. To test metformin’s effect on low-grade prostate cancers, the researchers gave metformin to mice with low levels of the NKX3.1 protein, which tend to develop prostate cancer and “mimic the progression of lower-grade to higher-grade prostate cancer, similar to cancers.” found in men under active surveillance, but by using metformin, we were able to stop further progression of the cancer,” Papachristodoulou said.

The researchers then looked at human prostate cancer cells and tissues and confirmed that metformin acts on the same mitochondrial processes in humans and prevents further cancerous changes.

“The work was very elegant,” says Stein. “The models they developed to understand the disease were fundamental to answering this question. Finding a completely new mechanism of action for a ubiquitous drug is very extraordinary.”

Potential to help reduce prostate cancer disparities

Papachristodoulou says that metformin could be particularly beneficial for black men, because they are more likely than white men to develop aggressive prostate cancer, while others say that “although some health disparities are due to social, economic and health care inequalities, we “We believe that biological factors such as differences in NKX3.1 and mitochondrial levels also contribute.”

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