Research into diabetes drug for therapy of metastatic prostate cancer

2023-08-14 06:15:31

Vienna (OTS) – While patients with localized prostate cancer have a good chance of survival, mortality in those affected with progressive, metastatic prostate cancer remains high. The exact mechanism of tumor spread has not yet been sufficiently elucidated. An international research team led by MedUni Vienna has now decoded the underlying cellular signaling pathway and researched a common diabetes drug as a new treatment option. The study was recently published in the renowned journal Molecular Cancer.

When examining prostate cancer cells in a complex mouse model, the research team led by Lukas Kenner (Clinical Institute of Pathology at MedUni Vienna, Department of Laboratory Animal Pathology at Vetmeduni Vienna) identified the protagonists involved in regulating tumor cell growth and their interaction. The main role was played by the protein STAT3 (Signal Transducer and Activator of Transcription 3), whose activation by another protein (interleukin 6, IL6) has long been in the limelight of cancer research in connection with the progression of tumor diseases.

“In our study, we were able to show for the first time that, interestingly, permanent activation of STAT3 prevents the development of prostate cancer and the development and spread of metastases. Conversely, we found that the loss of the signaling pathway between STAT3 and IL6 in the prostate can lead to massive tumor growth and metastases, which significantly increases the aggressiveness of the cancer and the mortality rate,” study leader Lukas Kenner summarizes the core of the results.

Possible drug already available
As was also found in the course of the study, the activation of STAT3 in the prostate leads to an increased occurrence of cell components (LKB1/pAMPK) that are responsible for the regulation of sugar metabolism and are associated with type 2 diabetes mellitus. The proteins LKB1/pAMPK block certain cancer molecules (mTOR and CREB) and thus also tumor growth. “As a consequence, we used a common diabetes drug in our research work,” says Lukas Kenner. It was discovered that the drug metformin, which is used in type 2 diabetes to regulate glucose levels, can significantly slow the progression of STAT3-positive prostate cancer. STAT3-positive prostate cancer has a metabolism very similar to type 2 diabetes. “Since metformin is already available, our research results might help to develop new treatment options for patients with STAT3-positive prostate cancer in the foreseeable future,” says Kenner ahead of further research on the newly discovered therapy option.

Most common cancer in men
Since 1994, prostate cancer has been the most common cancer in men in Austria, ahead of lung cancer (Statistics Austria 2022). In 2019, 6,039 new cases and 1,352 deaths from prostate cancer were registered. The tumors in the so-called prostate gland in men remain localized in the majority of cases and are therefore easily treatable. However, around 20 percent of patients develop metastatic prostate cancer, which is still considered incurable. Worldwide, the malignant disease of the prostate (following lung cancer) is the second leading cause of cancer-related death in men.

Publikation: Molecular Cancer
STAT3/LKB1 controls metastatic prostate cancer by regulating mTORC1/CREB pathway
Jan Pencik, Cecile Philippe, Michaela Schlederer, Emine Atas, Matteo Pecoraro, Sandra Grund-Gröschke, Wen (Jess) Li, Amanda Tracz, et.al., Marcus Hacker, Lukas Kenner
Doi: 10.1186/s12943-023-01825-8;

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