A recent study published in the Journal of Biological Chemistry showed that a specific combination of drugs can effectively suppress the growth of late-stage prostate cancer. The study is entitled “Inhibition of Polo-like Kinase 1 (Plk1) Enhances the Antineoplastic Activity of Metformin in Prostate Cancer”.
Prostate cancer is the second most common cancer among men in the U.S. It is curable, but there are limitations in the treatment of late-stage prostate cancers.
Suppression of the male sex hormone – androgen – is one of current treatment therapies applied in prostate cancer patients; this treatment is known as castration. However, in certain situations, castration can result in a more robust cancer, as it has the capacity to enhance oxidative stress within the prostate, increasing the expression of the Plk1 (Polo-like kinase 1) gene and, subsequently, androgen production. Over-expression of the Plk1 gene has been observed in several cancers.
“The goal of castration is to block androgen synthesis,” explained the study’s lead author Dr. Xiaoqi Liu in a news release. “But cancer cells eventually become ‘smart’ enough to make androgen anyhow, which is why the cancer continues to grow.” Castration can also disturb the body’s metabolism causing insulin resistance, which can induce androgen synthesis; cancer will continue to grow if these two side effects are not blocked, explained Dr. Liu.
Researchers found that a low-dose combination of metformin and BI2536 can block the proliferation of prostate cancer cells that withstand all available treatments, potentially prolonging the life of patients. These findings were observed in both prostate cancer cell culture assays and in mice models of advanced human prostate cancer.
Metformin is a commonly used oral antidiabetic drug that has been previously shown to have a strong antineoplastic action in several tumors including prostate cancer. Likewise, BI2536 is a compound with potential antineoplastic activity, known to inhibit the gene Plk1, which has been associated with several cancers. The team believes that treatment with this combination of drugs induces self-destruction of tumor cells and suppresses androgen production.
“We’ve found a promising way to treat late-stage prostate cancer,” said Dr. Liu. “By combining low levels of two well-tolerated drugs, the progression of this disease could be significantly delayed. Completely curing the cancer at the advanced stage is pretty much impossible, but this treatment might manage it for a while – that’s exciting.”
Still, according to Dr. Liu, a “key finding” of the study lies within the fact that the drugs had no effects on healthy prostate cells. “Ideally, cancer therapy will have minimal effects on normal cells.” Testing both drugs in clinical trials as a combination therapy is the team’s future goal.
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