Research into Use of Diabetes Medication for Treatment of Metastatic Prostate Cancer

Patients with localised prostate cancer have a good chance of survival, but mortality rates among those with advanced, metastatic forms of the condition remain high. 

Until now, the precise mechanism behind the spread of the tumour has not been fully explained. But an international research team headed by MedUni Vienna has succeeded in decoding the underlying cellular signal pathway and has carried out research using a common diabetes medication that could provide a new treatment option. 

The study has just been published in the journal Molecular Cancer.

Using a complex mouse model, the research team under Lukas Kenner (MedUni Vienna Department of Pathology, Department of Laboratory Animal Pathology at Vetmeduni Vienna) examined prostate cancer cells and identified the key factors in the regulation of tumour cell growth and the way they interact with each other. 

The protein signal transducer and activator of transcription 3 (STAT3) plays the leading role — its activation by another protein called interleukin 6 (IL6) has been a focus for cancer researchers in connection with tumour progression for some time now.

In the course of the study, the researchers also found that activation of STAT3 in the prostate leads to increased levels of cell components (LKB1/pAMPK) that are responsible for the regulation of glucose metabolism and are linked to type 2 diabetes mellitus. 

The proteins LKB1/pAMPK block certain cancer molecules (mTOR and CREB) and as a result also stop the tumour growing. 

“In light of this finding, we used a common diabetes drug in our research,” said Kenner. 

Kenner and his team discovered that the active ingredient metformin, which is used in the treatment of type 2 diabetes to regulate glucose levels, can significantly slow the progression of STAT3-positive prostate cancer, a condition with a metabolism that is very similar to type 2 diabetes.

Prostate cancer has been the most common type of cancer in men in Austria since 1994, followed by lung cancer (Statistics Austria, 2022). In 2019, 6,039 new cases and 1,352 deaths due to prostate cancer were recorded. 

In the vast majority of cases, tumours in the prostate gland remain localised, meaning that they can be treated effectively. However, about 20% of patients develop metastatic prostate cancer, which is still incurable. Malignant prostate tumours are the second most common cause of cancer-related death in men worldwide (after lung cancer).

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Sources:

Jan Pencik, Cecile Philippe, Michaela Schlederer, Emine Atas, Matteo Pecoraro, Sandra Grund-Gröschke, Wen Li, Amanda Tracz, Isabel Heidegger, Sabine Lagger, Karolína Trachtová, Monika Oberhuber, Ellen Heitzer, Osman Aksoy, Heidi A. Neubauer, Bettina Wingelhofer, Anna Orlova, Nadine Witzeneder, Thomas Dillinger, Elisa Redl, Georg Greiner, David D’Andrea, Johnny R. Östman, Simone Tangermann, Ivana Hermanova, Georg Schäfer, Felix Sternberg, Elena E. Pohl, Christina Sternberg, Adam Varady, Jaqueline Horvath, Dagmar Stoiber, Tim I. Malcolm, Suzanne D. Turner, Eileen E. Parkes, Brigitte Hantusch, Gerda Egger, Stefan Rose-John, Valeria Poli, Suneil Jain, Chris W. D. Armstrong, Gregor Hoermann, Vincent Goffin, Fritz Aberger, Richard Moriggl, Arkaitz Carracedo, Cathal McKinney, Richard D. Kennedy, Helmut Klocker, Michael R. Speicher, Dean G. Tang, Ali A. Moazzami, David M. Heery, Marcus Hacker, Lukas Kenner. STAT3/LKB1 controls metastatic prostate cancer by regulating mTORC1/CREB pathway. Molecular Cancer, 2023; 22 (1) DOI: 10.1186/s12943-023-01825-8 

Medical University of Vienna. (2023, August 14). Research into use of diabetes medication for treatment of metastatic prostate cancer: Active ingredient metformin can significantly slow the progression of STAT3-positive prostate cancer. ScienceDaily. Retrieved August 14, 2023 from www.sciencedaily.com/releases/2023/08/230814122018.htm
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