Why a diabetes medication could fight cancer

Diabetes
When I started doing some research on this topic I found it very suprising that diabetes had already been described in Egypt about 3000 years ago (Source). More than 80 years ago, the difference between diabetes mellitus (DM) type 1 and type 2 was established.

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DM2 has been characterized quite clearly. It is the most common form of diabetes which shows insulin-resistance, hyperglycemia (excess amount glucose in the blood) and distinct lack of insulin (Source). DM2 is often caused by a combination of genetic interactions and environmental factors (Source).

Diabetes and cancer?

Now it might not seem obvious that a diabetes medication could help against cancer as one could assume that these two diseases have nothing in common. This however, is not true. Quite interestingly, researchers could observe that the tumour microenvironment shows characteristics of abnormal cellular metabolism (Source). Which is also the case for diabetes, given the impairment of the glucose/insulin metabolism. Researchers are still trying to understand the genetics underlying these diseases (Source).

Metformin

A commonly prescribed drug for DM2 is called metformin. It has ben characterized quite well, it is safe and has no severe side-effects (Source, Source).

Structure of metformin

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So how does metformin work? Metformin was shown to inhibit the mitochondrial oxidative phosphorylation complex I, thereby decreasing the ATP synthesis (Source).
Consequently, AMP-activated protein kinase (AMPK) a energy sensor becomes activated that causes metabolic changes within the cell. Those include increased glycolysis, stronger lactate production and reduced activity of the citric acid cycle (Source).

How is metformin related to cancer?

In a way, this is related to head and neck squamous cell carcinoma (HNSCC). Various studies observed that patients having HNSCC which were treated with metformin had better outcomes (Source).
A recent study (Source) now tried to determine whether metformin can alter cellular metabolism in tumours and if it can induce apoptosis in cancer cells. In total, they treated 39 patients. The first thing that researchers observed was that apoptosis (induced cell death) of carcinoma cells noticeably increased. Secondly, metformin due to its function was able to cause changes in the tumour microenvironment which had deleterious effects on the cancer’s energy supply. Since one feature of cancer cells is their rapid proliferation, they also require enormous amounts of energy. If this energy demand cannot be covered, the tumour cannot grow or only slowly.
Although metformin cannot kill cancer cells on its own, combining it with other therapeutical drugs might improve the outcome for many patients with HNSCC.