Just like the body’s cells, cancer cells need energy like the sugar molecule, glucose. Researchers have long been interested in finding out if it is possible to “starve” cancer cells by preventing sugar uptake. It is also known that some cancer cells increase their intake of sugar molecules as a survival strategy, which can reduce the effect of treatment. Would it be possible to prevent glucose from entering the cancer cell and in that way increase the effect of chemotherapy?
This is what researchers at Lund University and the University of Pisa have studied.
To enable sugar molecules to enter the cancer cell through the cell membrane, the cell uses so-called sugar transporters, which can be likened to swing doors that let substances in and out. In total, the researchers can currently identify 14 such sugar transporters. In the present study, the researchers investigated number 1, GLUT1, and its role in acute myeloid leukaemia (AML).
By introducing specially designed inhibitors – substances that prevent or impede activities in the cell membrane – the researchers succeeded in blocking 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”, says Karin Lindkvist, Professor of Cell Biology at Lund University who led the study.
In the membrane of the cancer cells (above, left) there are sugar transporters, that can be likened to swing doors through which glucose enters the cancer cell (purple). Using specially designed inhibitors (above right, yellow areas) prevented sugar uptake (above left, purple areas) and the cancer cells became more sensitive to chemotherapeutics. Photo and illustration: Raminta Venskutonytė
The form of cancer the researchers studied, acute myeloid leukaemia, is one of the most common forms of leukaemia among adults. AML has a relatively poor prognosis and a high risk of relapse, above all among the elderly population, as they often cannot tolerate the tough treatment regime as good as younger patients can.
“Our hope is that combining chemotherapy with inhibitors that block the sugar uptake to the cancer cells, can improve the effect of the treatment and thereby cure more patients in the future”, states Anna Hagström, Senior Lecturer at the Division of Clinical Genetics, Lund University, and co-author of the study.
Understanding these proteins and how they regulate its swing doors is an important field of research, says Karin 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”, says Karin Lindkvist.
A lot of research remains to be done before it can be used in patients.
“The results need to be repeated both in experimental studies and clinical trials. My hope is that someone will take this further with the aim to treat patients suffering from AML or other cancer diseases that we know use GLUT1 transporters for sugar uptake”, she concludes.
Publication: Targeting GLUT1 in acute myeloid leukemia to overcome cytarabine resistance.
Karin Lindkvist, Professor of Cell Biology
+46 734 22 27 86
karin [dot] lindkvist [at] med [dot] lu [dot] se