According to the results of some preclinical trials, low doses of metformin, an antidiabetic drug, may effectively eliminate cancer stem cells, a group of cells believed to be responsible for tumor initiation, as well as tumor relapse, given that these cells are resistant to standard chemotherapies.
In combination with the standard chemotherapy for pancreatic cancer, metformin was observed to efficiently eradicate both cancer stem cells and more differentiated cancer cells that form the bulk of the tumor. The study was presented at the American Association for Cancer Research’s Pancreatic Cancer: Progress and Challenges conference in Lake Tahoe, Nev., from June 18-21, 2012 by Christopher Heeschen, M.D., Ph.D., a professor for experimental medicine at the Spanish National Cancer Research Centre in Madrid.
Heeschen said that the majority of clinical trials of pancreatic cancer during the last 15 years failed to demonstrate a notable improvement in the average survival, which indicates for various reasons the methods used in these trials were insufficient. However, within the last few years, scientists have discovered cancer stem cells, which contrary to the cancer cells that make up the bulk of the tumor, consist of a small subset of cells that are resistant to conventional therapy.
“Therefore, efficiently targeting these cells will be crucial for achieving higher cure rates in patients with pancreatic cancer. Our newly emerging data now indicate that metformin, a widely used and well-tolerated drug for the treatment of diabetes, is capable of efficiently eliminating these cells.”
The team discovered that metformin-pretreated cancer stem cells proved especially sensitive to changes to their metabolism through the activation of AMPK, as metformin killed the cancer stem cells, but only stopped the cell’s growth in more differentiated cancer cells.
“As the cancer stem cells represent the root of pancreatic cancer, their extinction by reprogramming their metabolism with metformin in combination with the stalling of the proliferation of more differentiated cells should result in tumor regression and long-term, progression-free survival.”
Their findings were supported in an experiment with mice, in which they treated immunocompromised mice that were implanted with various sets of patient-derived tumors with a combination of metformin and the standard chemotherapeutic treatment for pancreatic cancer, gemcitabine. The results were reduced tumors and a prevention of relapse in contrast to mice treated only with metformin or with gemcitabine.
Heeschen remarked: “Intriguingly, in all tumors treated with metformin to date, relapse of disease was efficiently prevented and there were no noticeable adverse effects.”
According to Heeschen, assessing metformin in pancreatic cancer is ready for clinical trials. The team is currently waiting for results from of a study that evaluated metformin as a maintenance treatment in patients with advanced pancreatic cancer, and even though this study was based on retrospective data, Heeschen is optimistic that these new results will show a highly efficient treatment strategy. He concludes: “Pending the results of this study, an important aspect for the future will be to investigate if all patients respond to metformin or whether some patients, due to distinct genetic alterations, may not respond to this metabolic reprogramming.”
Written by Petra Rattue