Drugs to fight cancer

Drugs to fight cancer


Robert Gustafsson, PhD student in biochemistry at Stockholm University, and Markel Martinez Carranza, exchange student from Spain who is working on a Bachelor’s degree project in biotechnology at Stockholm University, are part of a research team from five Swedish universities which has discovered a completely new method for treating cancer. The concept is described in the respected journal Nature and is based on inhibiting a specific enzyme, MTH1, which cancer cells, unlike normal cells, depend on for their survival.

Markel and Robert are conducting experiments at MAX IV Laboratory which may lead to the development of new medications that kill cancer without damaging healthy cells.

”In our recent article in Nature, we examined how different potential drugs bind with a particular protein. This teaches us more about how these drugs can be developed so that they are better adapted for bonding with specific proteins and the illness that the protein represents”, Robert explains.

The protein that Robert and Markel are experimenting with using beamline I911-MX is required for the growth of cancer cells. The protein destroys the residue in cancer cells which is created by the cell’s metabolism. In cancer cells, much more residue is produced as a result of their increased metabolism and rate of cell division. The residue, which consists of reactive oxygen compounds, can damage the building blocks of DNA and eventually cause programmed cell death.

Diagram of the structure of the protein MTHI and its interaction with the potential drug TH588 which inhibits the function of the protein in a cancer cell, causing it to die.
Diagram of the structure of the protein MTHI and its interaction with the potential drug TH588, which inhibits the function of the protein in a cancer cell, causing it to die.

“If we inhibit the protein so that it is unable to have any effect, then the cancer cells will die as so much residue is created which destroys the DNA in the cancer cells. The interesting thing is that it’s only the cancer cells that die, because the body’s healthy cells have other ways of dealing with the damaged DNA building blocks”, says Robert.

This property makes the drug extremely powerful. The drug is still in the testing stages, currently undergoing tests on mice and cancerous tumour cells outside the human body. The goal is to ensure that the drug behaves in the correct manner and targets the particular protein that it is intended for.

Various potential drugs are under constant development, and Robert’s and Markel’s team are hoping to begin clinical studies within 12–18 months.

“To achieve the atomic resolution required to see how the drug bonds with the protein, we need synchrotron light. Synchrotron light is a very strong X-ray light that allows us to see things at incredibly short distances, for example the distance between atoms in a protein”, says Robert.

Robert and Markel are part of Associate Professor Pål Stenmark’s group at Stockholm University. The group is responsible for the work of showing in atomic resolution how the various potential drugs bond with the protein by using X-ray crystallography. Without the information about the structure of the protein, which they discovered through their experiments at MAX IV Laboratory, it would be impossible to develop the drug that will enable revolutionary new ways of treating cancer.