A combination of metformin and a hypoglycemic diet.

Discovered the mechanism that can make the cancer cells die of hunger: a combination of metformin and a hypoglycemic diet

The results of an Italian study published in Cancer Cell clearly demonstrate this.

Milan, 2 May 2019 - A group of researchers coordinated by Saverio Minucci, Director of the New Drugs Program of the European Institute of Oncology and Full Professor of General Pathology at the University of Milan in collaboration with the group of Marco Foiani, (Scientific Director of IFOM and Professor of Molecular Biology at the University of Milan), discovered an unprecedented molecular mechanism capable, if activated, of making cancer cells die of "hunger". The results funded by the AIRC Foundation for cancer research, appear today in the prestigious scientific journal Cancer Cell.

This is a new strategy to fight cancer by attacking its altered metabolism. Researchers have discovered that a diet that leads to a lowering of blood sugar, associated with the administration of metformin, triggers a chain reaction that, involving the  tumour suppressor PP2A, leads to the death of cancer cells. Metformin is a drug already widely used to treat type II diabetes. A multi-centre clinical trial, to test the tolerability of the combination and to gain preliminary data on the effectiveness of the metformin and a hypoglycemic diet in halting tumor progression in patients undergoing chemotherapy will start shortly. Previous studies have already shown that patients on chemotherapy treatment tolerate both glycemic reduction and metformin intake well.

"It is well known that metabolism is one of the key differences between cancer and healthy cells - explains Minucci - and therefore it must be possible to kill cancer cells by exploiting this difference. Cells use two processes to generate energy: glycolysis, based on the availability of glucose, and oxidative phosphorylation, which can be inhibited with metformin. The phenomenon of "metabolic plasticity" allows cells to adapt their metabolism depending on nutrient availability, switching from glycolysis to oxidative phosphorylation and vice versa.

In fact, by reducing the glycemic index by diet, in combination with metformin, we were able to inhibit the metabolic plasticity and kill the cancer cells. To better understand what is going on we examined the mechanism of the synergistic effect of diet and metformin. Thanks to a detailed functional analysis at the molecular level, we discovered that what kills the cancer cell is the activation of the PP2A protein and its molecular circuit. This is an important fact not only from the scientific point of view, but also useful for the clinic. We hypothesize that patients who present a mutation in this circuit may not respond to future therapy with diet and metformin ". "We are in a position to start clinical trials immediately - concludes Minucci -, and this rapid passage is very rare in the transition from basic research to the clinic, and is for us a source of great satisfaction and expectation for future developments”.


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