Could common diabetes drug slow down aggressive prostate cancer?
CANCER DIGEST – Dec. 16, 2023 – A new study shows that men whose prostate tumors have low levels of a certain gene are both more likely to develop aggressive cancer and to respond to the diabetes drug metformin.
The two-part study led by Alex Papachristodoulou a research scientist in the lab of Cory Abate-Shen, PhD at Columbia University showed that prostate tumors that were deficient in a protein produced by the NKX3.1 gene tended to become aggressive and metastatic, and that metformin slowed the progression of those tumors. The study results appeared in the Aug. 31, 2023 journal of European Urology.
NKX3.1 is a prostatic tumor suppressor gene located on chromosome 8p. A number of studies have shown that NKX3.1 protein is present in the majority of primary prostate tumors, it has been shown to be downregulated or producing low levels of the protein in many high-grade prostate cancers and is entirely absent in the majority of metastatic prostate cancers.
In the first part of the study, the research team looked at the effect of metformin on mice with prostate cancer, but with low levels of NKX3.1 and mice whose tumors had high levels of the protein.
They found that only the mice with low levels of the protein saw tumor growth slowed when administered metformin. The researchers then confirmed this finding in laboratory samples of prostate tumors taken from men.
“These mice mimic the progression from lower- to higher-grade prostate cancer, similar to the cancers found in men who are put on active surveillance,” Papachristodoulou said in a press release, “but with metformin, we were able to stop further progression of the cancer.”
The second part of the study involved an analysis of data from two studies of men who had radical prostatectomies. The tissue samples of those men were re-examined for NKX3.1 status and treatment for diabetes.
What they found was that the three out three men whose tumors were deficient in the gene and were treated with metformin were downgraded during follow-up, while three out of four men who did not take metformin had their cancers upgraded.
Papachristodoulou and Abate-Shen are now working with collaborators to set up a clinical trial to test if metformin can prevent the progression of prostate cancer in men with newly diagnosed, low-NKX3.1 tumors who are under active surveillance.