Imma Perfetto
Cosmos science journalist
A question that has puzzled oncologists for 30 years has been solved by researchers, who say their findings have implications for increasing the efficacy of radiation therapy.
Radiation therapy works by damaging the DNA in cancer cells to trigger cell death. But not all cancerous cells inside of a tumour die in the same way following radiotherapy and, until now, scientists weren’t sure why.
The findings are published in a new Nature Cell Biology study.
“The surprising result of our research is that DNA repair, which normally protects healthy cells, determines how cancer cells die following radiotherapy,” says Professor Tony Cesare, head of the Genome Integrity Unit at Children’s Medical Research Institute in Australia.
“The DNA inside our cells is constantly experiencing damage, and DNA repair is happening all the time to fix that and keep our cells healthy.
“Now, however, it seems these repair processes can recognise when overwhelming damage has occurred (e.g., from radiotherapy), and instruct a cancer cell how to die.”
The team used live cell microscope technology to follow irradiated cells for a week following radiation therapy. They found that when DNA damage was repaired by a method called “homologous recombination” cancer cells died during mitosis (cell division).
“Critically, death during cell division goes unnoticed by the immune system, so it won’t activate an immune response,” says Cesare. “This is not what we want.”
They found that cells using other DNA repair methods survived the cell division process but did so by releasing byproducts of DNA repair into the cell.
“To the cell, these repair byproducts look like a viral or bacterial infection,” says Cesare. “This causes the cancer cell to die in a manner that alerts the immune system. Which is what we do want.”
Associate Professor Harriet Gee, a radiation oncologist from the Western Sydney Local Health District Radiation Oncology Network who co-led the project, says these findings answer a clinical question that has puzzled the field for 30 years.
“The manner in which tumour cells die after radiotherapy depends on the engagement of specific DNA repair pathways, particularly when radiation is given at very high, focussed doses,” she says.
The finding suggest that it could be possible to force cancer cells treated with radiotherapy to die in a way that alerts the immune system.
“This opens up new opportunities to enhance radiation efficacy through combination with other therapies, particularly immunotherapy, to increase cancer cures,” says Gee.
