Researchers at Weill Cornell Medicine – Qatar (WCM-Q) may have found a therapy for multiple types of cancer using a widely-used diabetes drug.
Writing in the journal Cancers, the scientists believe that the drug metformin may have anti-cancer properties when used in conjunction with other therapies.
Dr Samson Samuel, research associate in physiology and biophysics at WCM-Q and lead researcher on the paper, said the investigation was initiated after it was noticed that diabetics using metformin to control their condition have lower instances of certain types of cancer, such as breast cancer, colorectal cancer, pancreatic cancer and prostate cancer, all of which are of particular concern in the Middle East.
Work began to examine the phenomenon in the laboratory using cells. According to Dr Samuel, they looked first at how the cells would respond to metformin, and did not see a huge effect. However, he said that when cells were starved of glucose and then treated with metformin, they began to produce an anti-angiogenetic protein called thrombospondin-1.
Angiogenesis refers to the formation of new blood vessels from the existing vascular system. Every part of the body needs a supply of blood to keep it fed and growing. When a tumour grows, this also has to be fed by blood vessels in a process called tumour angiogenesis. So, if this process can be inhibited or stopped, using an anti-angiogenetic drug, the tumour should either slow its growth or die.
However, Dr Samuel said that physicians cannot completely starve a cancer patient of glucose, so instead, the metformin was used in combination with molecule 2-deoxyglucose which inhibits the utilisation of glucose by the cells.
Working with the microvascular endothelial cells of mice – endothelial cells being those that line the inside of blood vessels – the research team found that the cells began to produce the anti-angiogenetic thrombospondin-1 when treated with a combination of 2-deoxyglucose and metformin. This effect was not seen in cells treated with either 2-deoxyglucose or metformin alone.
Dr Chris Triggle, professor of pharmacology at WCM-Q and the lead principal investigator for the study, said this is really significant. People who are diabetic and overweight have a higher risk for developing cancer and so the fact that metformin also potentially has the ability to treat cancer as well as diabetes means that physicians may be able to address the extra risk by reducing the blood glucose levels in a patient.
Dr Samuel added that they also have to look at how metformin targets other types of cells. He said that the study focused specifically on endothelial cells, but is looking forward to see the effect – if any – on breast cancer cells.
These results are of particular importance to the wider population because of the potential they hold for the treatment of cancer in general. Different therapies usually only target specific cancers – a breast cancer drug at a particular dosage may not work on another type of cancer, for example – but the drug combination of 2-deoxyglucose and metformin, owing to the production of the anti-angiogenetic protein thrombospondin-1 could allow the researchers to target the tumour angiogenesis associated with a range of cancers. Drug combinations may also allow them to reduce the need for toxic drugs or reduce the quantity they are administered in.
It is obviously too early to predict with any certainty, but it does offer hope for the future.
