Researchers at Lund University in Sweden have successfully increased cancer cells’ sensitivity to chemotherapy by preventing sugar uptake. Their study, “Targeting Glut1 In Acute Myeloid Leukemia To Overcome Cytarabine Resistance,” is published in Haematologica.
It is true that sugar feeds every cell in our body, even cancer cells. Researchers have long wondered if it would be possible to prevent glucose from entering the cancer cell and in that way increase the effect of chemotherapy.
To enable sugar molecules to enter the cancer cell through the cell membrane, the cell uses glucose transporters (GLUTs), which allow substances in and out. Researchers decided to study GLUT1 and its role in acute myeloid leukemia (AML).
Researchers decided to study acute myeloid leukemia as a distinct glucose metabolic signature was recently described showing that enhanced glycolysis correlates with decreased sensitivity for chemotherapy and poor prognosis.
GLUT1 is an integral membrane protein consisting of 12 transmembrane helices and an
intracellular domain, which transports glucose depending on the concentration gradient. Measuring activity of membrane proteins such as GLUT1 can be challenging due to lack of an easily accessible readout. The researchers developed a system where purified glucose transporters were reconstituted in vitro into giant vesicles reporting their transport activity using fluorescence microscopy, which allowed glucose uptake to be measured without any interference from other proteins.
By introducing specially designed inhibitors, the researchers succeeded in preventing sugar uptake to the cancer cells.
“We then examined whether the effect of the chemo used in the treatment of AML was improved when we blocked the sugar uptake. It was clear that the cancer cells became far more sensitive to the chemo drugs,” stated Karin Lindkvist, professor of cell biology at Lund University and leader of the study.
The researchers hope that the combination of chemotherapy and inhibitors that block sugar uptake to the cancer cells can improve treatment and help cure more patients in the future.
“Understanding these proteins and how they regulate its swing doors is an important field of research,” explained Lindkvist.
“Membrane proteins are targets of interest in the development of new treatments and it is commonly known that around half of all drugs on the market today target membrane proteins. There is a lot happening in the cell, and these proteins control what goes in and out of the cell. This particular sugar transporter appears to play a key role, as it is highly effective at helping the cell to take up sugar. It is also why the cancer cells make more of this transporter in order to obtain more energy,” said Lindkvist.
More research is needed before it can be used in patients, but these findings open a door of understanding and treatment options for patients suffering from AML or other diseases that use GLUT1 for sugar uptake.