Metastatic prostate cancer is often treated with a combination of methods, including hormone therapy, chemotherapy, immunotherapy, and targeted medicines. These treatments try to delay the growth of cancer and manage its symptoms.
Patients with localized prostate cancer have a fair chance of survival, but mortality rates for those with advanced, metastatic forms of the disease remain high. Until now, the specific process underlying tumor spread has not been fully defined. However, an international research team led by MedUni Vienna has succeeded in decoding the underlying cellular signal system and has conducted studies using a common diabetes medicine that could provide a new therapeutic option. The study was recently published in the journal Molecular Cancer.
Using a complex mouse model, the research team led by Lukas Kenner (MedUni Vienna Department of Pathology, Department of Laboratory Animal Pathology at Vetmeduni Vienna) examined prostate cancer cells to identify key factors in the regulation of tumor cell growth and how they interact with one another.
Intriguingly, our study found that permanently activating STAT3 prevents the development of prostate cancer as well as the development and spread of metastases for the first time. In contrast, we discovered that in the prostate, the loss of the signal pathway between STAT3 and IL6 can lead to massive tumor growth and metastasis, which significantly increases the aggressiveness of the cancer and the mortality rate.
Lukas Kenner
The protein signal transducer and activator of transcription 3 (STAT3) takes the lead; its activation by another protein termed interleukin 6 (IL6) has long been a focus for cancer researchers in relation to tumor growth.
“Intriguingly, our study found that permanently activating STAT3 prevents the development of prostate cancer as well as the development and spread of metastases for the first time.” In contrast, we discovered that in the prostate, the loss of the signal pathway between STAT3 and IL6 can lead to massive tumor growth and metastasis, which significantly increases the aggressiveness of the cancer and the mortality rate,” summarized principal investigator Lukas Kenner.
Potential medication already available
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,” stated Kenner. Kenner and his colleagues discovered that the active ingredient metformin, which is used to manage glucose levels in type 2 diabetes treatment, can considerably reduce the progression of STAT3-positive prostate cancer, a disorder with a metabolic remarkably similar to type 2 diabetes. “Because metformin is already available, our research findings could be useful in developing new treatment options for patients with STAT3-positive prostate cancer in the near future,” Kenner said, anticipating additional research into the newly discovered technique.
Most common form of cancer in men
Since 1994, prostate cancer has been the most prevalent type of cancer in Austrian men, followed by lung cancer (Statistics Austria, 2022). In 2019, there were 6,039 new cases and 1,352 deaths from prostate cancer. Tumors in the prostate gland stay localized in the vast majority of instances, allowing for successful treatment. Approximately 20% of individuals, however, develop metastatic prostate cancer, which is still incurable. Malignant prostate tumors are the world’s second leading cause of cancer-related mortality in males (behind lung cancer).
