Metformin (Glucophag) reduces the growth of pancreatic cancer
Investigators supported by the Hirshberg Foundation, including dr Kisfalvi (a recipient of a seed grant from the Foundation), Dr. Eibl (Hirshberg Laboratories at UCLA) and Dr. Rozengurt (the Hirshberg Chair in Pancreatic Cancer Research) have shown that metformin, the most widely prescribed drug for the treatment of type 2 diabetes mellitus, inhibit pancreatic cancer growth in preclinical animal models and human pancreatic cancer cells in culture. As the current therapies for pancreatic cancer offer very limited survival benefits, novel therapeutic strategies are urgently required to prevent and treat this aggressive disease. The recent studies of the team headed by Dr. Rozengurt have just appeared in the prestigious journal Cancer Research (see reference, below), as the first publication on the mechanism of metformin in human pancreatic cancer.
The new results assume an added importance in view of the fact that metformin is an FDA-approved drug (Glucophag) currently used in the treatment of type 2 diabetes mellitus. Additional interest in the new research is provided by recent epidemiological studies indicating that administration of metformin reduces the incidence and improves prognosis in pancreatic cancer patients. For example, a recent epidemiological report linked administration of metformin with a 62% reduced risk of pancreatic cancer in patients with type-2 diabetes mellitus (Li D, Yeung SC, Hassan MM, Konopleva M, Abbruzzese Gastroenterology. 2009; 137: 482-8.). Epidemiological studies from other groups from the UK also confirmed that metformin therapy (but not other antidiabetic drugs in use) is associated with greatly reduced risk of pancreatic cancer. However, epidemiological studies can not define the precise mechanism(s) by which metformin inhibits the proliferation of cancer cells. Indeed, it was not known whether metformin has any direct effect on pancreatic cancer growth. The recent work of the team headed by Dr. Rozengurt shows that metformin disrupts a crosstalk between insulin receptor and other growth-factor signaling systems in human pancreatic cancer cells. The most interesting piece of new information is that administration of metformin markedly inhibited the growth of human pancreatic cancer cells in animal models.
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The new results in Cancer Research provide a plausible mechanism for the beneficial effect of metfomin seen in diabetic patients and provide a rationale for influencing clinical practice in the management of conditions (including obesity and type 2 diabetes mellitus) that increase pancreatic cancer risk. Specifically, in the light of the new research, metformin should be selected as a first choice in the treatment of type 2 diabetes mellitus (as prevention for developing cancer) and should be considered to be included in the design of novel therapeutic strategies for pancreatic cancer.
Reference: Kisfalvi K, Eibl G, Sinnett-Smith J, Rozengurt E. Metformin disrupts crosstalk between G protein-coupled receptor and insulin receptor signaling systems and inhibits pancreatic cancer growth. Cancer Research 2009; 69: 6539-45.