Researchers of the Children’s Medical Research Institute in Sydney (Australia) have resolved a ancient mystery in cancer treatment: why cancer cells die in different ways after radiation therapy. This revolutionary discovery, published in ‘Nature Cell Biology‘, could significantly improve therapeutic strategies and increase cure rates.
The study reveals that the way cancer cells repair their DNA determines how they die after receiving radiotherapy.
Radiotherapy is a key cancer treatment that kills tumor cells by damaging their DNA. However, for decades, scientists have observed with bewilderment that cells from the same tumor can die in different ways. This finding is fundamentalsince certain types of cell death do not activate the immune system, while others trigger an immune response that helps eliminate remaining cancer cells. Boosting this immune response is one of the main objectives of cancer therapies.
“The surprising result of our research is that DNA repair, which normally protects healthy cells, determines how cancer cells die after radiotherapy,” he explains. Tony Cesare.
Under normal conditions, the DNA in our cells is constantly damaged and repaired to maintain cellular health. However, when the damage is severe, as in the case of radiotherapy, DNA repair processes dictate the fate of the damaged cells.
Cancer cells that repaired their damaged DNA using a method called homologous recombination tended to die during the process of cell division (mitosis). Unfortunately, this type of death does not activate the immune system, leaving the cancer undetected.
On the other hand, cells that repaired their DNA using alternative methods released byproducts that the body recognizes as signs of a viral or bacterial infection. This triggered an immune response that not only eliminated the cancer cells, but also alerted the immune system to attack other tumor cells.
Mitosis
The team showed that blocking homologous recombination changes the way cancer cells die, causing a death that activates a strong immune response. This strategy could be especially effective in cancers with mutations in the BRCA2 gene, which is essential for homologous recombination and is linked to breast cancer.
“Our discoveries open the door to combining radiotherapy with drugs that block homologous recombination», says Cesare. “This would force cancer cells to die in a way that activates the immune system, improving treatment outcomes.”
We’ve solved a question that has baffled researchers for 30 years
These findings were made possible by advanced live cell microscopy technologies, which allowed researchers to observe irradiated cells for a week. “The real-time image showed us the complexity of the results after radiotherapy and allowed us to identify the mechanisms behind the different types of cell death,” says Cesare.
Associate Professor Harriet Gee, radiation oncologist and co-leader of the project, highlights the clinical relevance of the study. « We have solved a question that has baffled researchers for 30 years. Understanding how specific DNA repair pathways influence tumor cell death opens new opportunities to enhance the effectiveness of radiotherapy, especially in combination with immunotherapyto increase cancer cure rates.
This breakthrough not only solves a crucial scientific puzzle, but also offers hope for more effective cancer treatments, bringing researchers one step closer to higher cure rates worldwide.
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