"This is a significant discovery. For the first time, we have clinical observations showing that prostate cancer patients with diabetes who received drugs targeting the protein remained relapse-free during the period we followed them," lead author of the study, Lukas Kenner, visiting professor at Umeå University in Sweden, said in a press release.
A previous study found that men with diabetes and elevated levels of hemoglobin A1c- a marker of glycemic control- may have a lower risk of developing prostate cancer. Research also shows that a class of anti-diabetes drug, thiazolidinediones (TZDs), is linked to a lower risk of prostate cancer, suggesting potential for these drugs in preventing the disease.
TZDs are synthetic insulin sensitizers that act as agonists to the peroxisome proliferator-activated receptor gamma (PPARy), a nuclear receptor protein frequently found in adipose tissue or spleen, where it plays a key role in adipogenesis and energy balance.
In the current study, researchers investigated the common and specific pathways targeted by three PPAR agonists: Bezafibrate, Tesaglitazar, and Pioglitazone in primary and metastatic prostate cancer cells. Their analysis included cellular and mouse studies, as well as a retrospective study of 69 patients with prostate cancer and type 2 diabetes, followed by researchers at the Medical University of Innsbruck between 2014 and 2023.
Ultimately, the researchers found that pioglitazone inhibits prostate cancer cell growth and drives metabolic reprogramming of cancer cells, thus weakening their ability to grow. Meanwhile, from the retrospective human study, they found that patients with diabetes and prostate cancer who were treated with PPAR agonists post-radical prostatectomy remained relapse-free over a 5-10 year follow-up period.
"The findings are very promising, but further clinical studies are needed to both confirm the results and to investigate whether the treatment can also be used in patients with prostate cancer who do not have diabetes," said Kenner.
Sources: EurekAlert, Molecular Cancer