Chemotherapy can save lives, but it can also leave lasting damage behind. New research suggests one protein might help tip that balance.
According to Mirage News, researchers at the University of Sheffield and UT Southwestern Medical Center studied TOP2 poisons, a group of chemotherapy drugs used against fast-dividing cancer cells. The drugs interfere with enzymes cells need to keep dividing, causing major DNA damage that kills them.
The problem is that the effect does not stop at tumors. Non-dividing healthy cells, including neurons in the brain and cardiomyocytes in the heart, also use these enzymes, which puts them at risk of injury.
In a study published in Molecular Cell, the researchers identified the stress-response protein HSF1 as a selective factor that appears to affect TOP2B but not TOP2A. According to the report, rapidly dividing cancer cells use both enzyme forms, while some healthy cells depend mostly on TOP2B. The researchers said that difference could point to a safer way to use the treatment.
Using atomic force microscopy, the team directly observed the proteins interacting with DNA. Dr Thomas Catley, postdoctoral research associate at the University of Sheffield’s School of Chemical, Materials and Biological Engineering, said: “It is incredible to be able to see how these proteins cling to DNA with nanometre precision.”
The study was done in vitro using cells extracted from mice, not in a human clinical trial. That means the findings are still early and do not change chemotherapy protocols for patients now.
According to Mirage News, in lab experiments, adding an HSF1 inhibitor greatly reduced toxicity in healthy, non-dividing cells while preserving the treatment’s ability to attack tumors. Ram Madabhushi, associate professor at UT Southwestern who led the research, said the finding suggests cells “preferentially regulate TOP2B over TOP2A in this manner.”
The researchers now plan to test whether combining TOP2 chemotherapy with HSF1 inhibition can protect healthy tissue without weakening the drugs’ anti-cancer effect. Madabhushi said: “We are currently testing whether combination therapy with HSF1 inhibitors can protect mice from the secondary toxicity of chemotherapy with TOP2 poisons.”
Catley said: “From this, we hope to discover new ways of treating cancer effectively.”
Read more from The Cool Down.
