In their quest to find new and better methods to make cancer cells more susceptible to treatment, Karin Lindkvist and her research group at Lund University in Sweden are looking into the world of molecules, using the X-rays at the MAX IV laboratory. The researchers believe that limiting the cells’ access to sugar will make cancer cells more sensitive to treatment.
Many of the cancer treatments used today were established in the 1980´s. In order to decrease mortality further, there is an urgent need for new ways to treat cancer. Researchers around the globe have taken on this challenge, including Karin Lindkvist and her team in Lund.
“We are combining structural biology with cell biology to find new molecular mechanisms that facilitate the development of new treatments for cancer”, says Karin Lindkvist.
The blood cancer Acute Myeloid Leukemia (AML) is the most common form of leukemia in adults and the second most common in children. Despite the introduction of new drugs, the overall cure rates remain around 20 per cent in adults and 65 percent in children. Emerging literature suggests that obesity is a risk factor for cancer. Obesity further reduces leukemia survival, and increases the risk of treatment-related complications, suggesting that leukemia cells residing in adipose tissue (fat cells) may be more resistant to treatment and therefore contribute to disease persistence. However, the nature of the interplay between leukemia cells and fat tissue is poorly understood.
“Leukemic stem cells have been shown to utilize the fat tissue microenvironment to support their metabolism, that is, they use the fat cell as energy and this helps them survive chemotherapy. We have preliminary data suggesting that leukemic cells become more sensitive to chemotherapy if we block their glucose uptake. Therefore, targeting the glucose uptake of the cancer cells may represent a new treatment for overcoming chemoresistance”, explains Professor Karin Lindkvist, group leader for a team of researchers at Lund University.
To perform this type of research, large amounts of human protein is required. Since one research obstacle is obtaining sufficient amounts of human protein, the researchers use the gene coding for the specific protein, for example a glucose (sugar) transporter, to duplicate it. Next, the protein must be well-packed into a crystal in order for the researchers to study the details of the protein structure and how the cancer drug is binding to it.
“We’re interested in blocking the sugar uptake of cancer cells, in order to improve cancer treatment. But in order to do so we need to know how the proteins look and thus how cancer drugs target them”, says Karin Lindkvist.
In their research the group utilizes the beamline facility at the MAX IV laboratory.
“A regular microscope isn´t powerful enough for looking closer at this type of proteins. So instead we expose the proteins to X-rays from the beamline. The light is dispersed and then we collect the reflections and calculate what the protein looked like in the crystal”, says Karin Lindkvist.
Soon a new beamline called MicroMAX will be built at MAX IV. This infrastructure addition will facilitate the collection of research data for Karin Lindkvist in that the crystals used can be much smaller.
Karin Lindkvist, Professor Medical Structural Biology
Your work has the potential to affect people’s lives. How does that make you feel?
– I think it’s crucial. That is really my driving force.
Is it possible to say when cancer patients might benefit from your research?
– No. Our research is still in a very early stage.
And now the big one: Will cancer ever be eradicated?
– No. In order to have evolution, you must have mutations, and with evolving cells there is always a risk for things going wrong. That´s the flip side of the coin when it comes to evolution and progress.
Text and photos by Agata Garpenlind Cronqvist