"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," says Lukas Kenner, visiting professor at Umeå University and one of the study's lead authors.
The protein that the researchers have studied is called PPARy, peroxisome proliferator-activated receptor gamma. In diabetes research, PPARy has been extensively studied in view of the protein's role in metabolic processes and insulin sensitivity.
What the research team, led by Professor Kenner, has now shown is that patients who were treated for prostate cancer and who also had diabetes, who were treated with drugs that regulate the PPARy protein, managed without recurrence of prostate cancer. In studies of cell cultures, researchers also observed that the drug in question, pioglitazone, not only inhibits the growth of prostate cancer cells but also drives a metabolic reprogramming of the cancer cells, weakening their ability to grow.
"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," says Lukas Kenner.
The research has been conducted as a combination of studies on cells and mice as well as a retrospective study of 69 prostate cancer patients with type 2 diabetes that was followed by the Medical University of Innsbruck in 2014 - 2023.
In certain types of cancer, PPARγ can contribute to tumour growth or metabolic changes. The drug, pioglitazone, is a so-called agonist that binds to a PPARy receptor and activates it. Thereby it modulates the signalling pathway and aims to counteract tumour-promoting effects by changing the cellular metabolism but may also reduce inflammation.
Atas E, Berchtold K, Schlederer M, Prodinger S, Sternberg F, Pucci P, Steel C, Matthews JD, James ER, Philippe C, Trachtová K, Moazzami AA, Artamonova N, Melchior F, Redmer T, Timelthaler G, Pohl EE, Turner SD, Heidegger I, Krueger M, Resch U, Kenner L.
The anti-diabetic PPARγ agonist Pioglitazone inhibits cell proliferation and induces metabolic reprogramming in prostate cancer.
Mol Cancer. 2025 May 5;24(1):134. doi: 10.1186/s12943-025-02320-y