DNA Repair Pathways Influence Cancer Cell Death After Radiotherapy, Study Finds

A new study published in Nature Cell Biology improves our understanding of why cancer cells die in different ways following radiotherapy. Researchers from the Children's Medical Research Institute (CMRI) have discovered that DNA repair mechanisms play a crucial role in determining how cancer cells respond to radiation treatment.

The research, led by Radoslaw Szmyd and Tony Cesare, revealed that when cancer cells use homologous recombination to repair radiation-induced DNA damage, they tend to die during cell division. This form of cell death goes unnoticed by the immune system. In contrast, when other DNA repair methods are employed, cancer cells may survive cell division but die later in a manner that triggers an immune response.

Professor Cesare explained, " “The surprising result of our research is that DNA repair, which normally protects healthy cells, determines how cancer cells die following radiotherapy." The team found that blocking homologous recombination could alter the way cancer cells die, potentially enhancing the immune system's response to the treatment.

The study also uncovered that cancer cells with mutations in the BRCA2 gene, which is important for homologous recombination, do not die during cell division after radiotherapy. This finding has implications for understanding the response of certain breast cancers to radiation treatment.

The researchers used advanced live cell microscopy to observe irradiated cells for a week, allowing them to unravel the complex outcomes following radiation therapy.

Harriet Gee, a radiation oncologist involved in the study, noted that these findings answer a clinical question that has puzzled the field for three decades. “We found that 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, focused doses. This opens up new opportunities to enhance radiation efficacy through combination with other therapies, particularly immunotherapy, to increase cancer cures.’’