Radiation therapy/ radiotherapy is the most important type of cancer treatment, in which beams of intense energy kill cancer cells. However, it remains obscure- how do tumor cells die after radiotherapy?
A new study shed light on this big mystery. Scientists at the Children’s Medical Research Institute (CMRI) suggest that DNA repair, which normally protects healthy cells, determines how cancer cells die following radiotherapy.
Our cells’ DNA is constantly getting damaged and repaired to stay healthy. But when there’s overwhelming damage, like from radiotherapy, these repair processes can tell a cancer cell to die.
When DNA damage from radiation therapy was repaired using homologous recombination, cancer cells died during cell division but didn’t trigger an immune response, which is not ideal.
However, when other DNA repair methods were used, cells survived cell division and released byproducts resembling viral or bacterial infections. This caused the cancer cells to die in a way that activated the immune system, which is the desired outcome.
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The team discovered that blocking homologous recombination caused cancer cells to die, which triggered a strong immune response. They also found that cancer cells with BRCA2 mutations, crucial for breast cancer and necessary for homologous recombination, do not die during cell division after radiotherapy.
This breakthrough solves a significant scientific mystery and opens the possibility of using drugs to block homologous recombination. By forcing cancer cells treated with radiotherapy to die, the immune system is alerted to their presence, signaling that the cancer needs to be destroyed.
Prof Cesare credits these breakthroughs to live cell microscope technology that enabled his team to follow irradiated cells for a week following radiation therapy. “Live imaging showed us the full complexity of outcomes following radiation therapy, allowing us to tease out exactly why this occurred.”
Co-project lead A/Prof Harriet Gee, a radiation oncologist from the Western Sydney Local Health District Radiation Oncology Network, said, “These findings answer a clinical question that has puzzled the field for 30 years.”
“We found that how tumor cells die after radiotherapy depends on the engagement of specific DNA repair pathways, particularly when radiation is given at high, focussed doses. This opens up new opportunities to enhance radiation efficacy through combination with other therapies, particularly immunotherapy, to increase cancer cures.”
Prof Cesare said Dr Szmyd worked for six years on this “tough nut to crack” and “The perseverance required for a project of this scope is a testament to Radek and the team. “Everyone is aware of patients battling cancer. Discovering something like this that has the potential to make a big difference to people’s lives is very rewarding.”
Journal Reference:
- Szmyd, R., Casolin, S., French, L. et al. Homologous recombination promotes non-immunogenic mitotic cell death upon DNA damage. Nat Cell Biol (2025). DOI: 10.1038/s41556-024-01557-x
