Cancer cells with specific genetic defect extra susceptible to therapy that damages DNA

Using a strategy based on treating cancer cells that carry a specific genetic signature - hyper-expression of the protein Myc - with therapy that affects the stability of the cell's DNA, more effective results can be achieved. This was discovered by Andreas Höglund in his dissertation to be publicly defended at Umeå University on September 9.

Today cancer is a public health disease that statistically afflicts every third Swede some time during their lifetimes. Although certain external factors such as smoking, obesity, and exaggerated sunbathing increase the risk of cancer, everyone can develop this disease, regardless of these factors. This is because during our lifetime we gather mutations in our genes that govern how the body's cells grow and multiply. Sometimes these mutations affect important cellular programs, entailing that a cell somewhere in the body receives a growth advantage that makes it grow and multiply until a tumor has been formed.

In his dissertation, Andreas Höglund shows that cancer cells that carry a specific genetic defect are extra susceptible to treatment that damages the cells' DNA.

"Cancer cells that express the protein Myc at unnaturally high levels are extra sensitive to these types of treatment," says Andreas Höglund.

Myc is a vital protein in the body that governs the reading of thousands of genes. Myc does not cause cancer until mutations lead to abnormally high levels of this protein, and further defense mechanisms are knocked out. Defective expression of Myc is one of the most common causes of cancer.

In the dissertation studies Andreas Höglund also maps signalling paths that govern the cell's ability to recognize and repair damaged DNA. In collaboration with pharmacuetical companies, small chemical compounds have been tested in the hope of being able to develop these beyond a preclinical setting. By steering the binding of these compounds to precisely those signal paths that govern the cell's ability to recognize and repair DNA damage, it was possible to neutralize the cancer cells.

"Directing treatment toward the signal paths we have identified is highly appropriate for cancer cells with high Myc levels. The hope is to be able to use the Myc signature in a number of cancer diseases in order to attain more specific treatment, which also has the potential of reducing side effects in comparison with current treatment methods," says Andreas Höglund.