Research Overview
Radio- and chemotherapy work by creating damage in the blueprints (DNA) of cancer cells, yet malignant cancers, such as glioblastoma (a tumor of the brain), regrow after treatment. Paradoxically, when treated tumors are examined, they don’t always have new driving mutations in their DNA, yet the cancer that grew back is somehow more resistant to therapy. This raises a basic open question in cancer biology: How did our treatment change the tumor?
We believe there are non-genetic chemical scars left on the blueprints on our cells from our therapy, and that the cancer cells use these scars to behave in a more aggressive manner. This theory has been challenging to study in laboratories because radio- and chemotherapy cause random damage, making their effects on exact locations in our DNA difficult to pinpoint. To get around this issue and understand how DNA damage might leave behind non-genetic scars, we designed systems in the lab that create DNA damage at pre-defined locations. With this technology, we now have a precise “map” of where damage occurred, enabling us to look back on DNA damage with greater clarity.
We have found that DNA damage does in fact leave behind non-genetic changes in the blueprints of cancer cells. These non-genetic changes include chemical modifications such as DNA methylation, changes in the organization and orientation of DNA, expression of genes, and many other changes. This is a discovery to follow-up on and study, as we believe cancer cells use these non-genetic changes to alter how they interpret and express the DNA, or blueprints, and behave in a more aggressive and treatment-resistant manner.
By understanding the process that leads to these alterations, we hope to find therapeutic strategies that block this process and disable the ability of cancer cells to adapt to our widely used therapies.