Researchers at the University of California, Irvine (UCI) have made a meaningful breakthrough in understanding how cancer cells react to DNA damage. Their findings, published in Nature Structural & Molecular Biology, detail a previously unknown mechanism that triggers an inflammatory immune response when cellular DNA is compromised. This discovery could pave the way for more effective and personalized cancer treatments.
The study focused on the intricate dance between DNA damage and the body’s immune system. when DNA is severely damaged, beyond the cell’s repair capabilities, a specific response is activated to prevent the damaged cell from becoming cancerous. This process involves a complex interplay of enzymes and proteins, a key player being the IRAK1 enzyme. Unlike previously understood mechanisms involving the ATM enzyme, this new pathway involves the release of the IL-1α protein, which travels to neighboring cells, triggering the IRAK1 protein and initiating an inflammatory response via NF-κB.
“This discovery could have significant implications for cancer treatment,” explains Rémi Buisson, UCI associate professor of biological chemistry and corresponding author of the study. “Understanding how different cancer cells react to DNA damage could lead to more tailored and effective therapies, perhaps reducing negative side effects and improving the quality of life for patients.”
The UCI team, led by postdoctoral fellow Elodie bournique and graduate student Ambrocio Sanchez, developed a sophisticated imaging technique to analyze this cellular response at the single-cell level. This allowed for precise measurement of how NF-κB is regulated, revealing the novel pathway involving IL-1α and IRAK1. The researchers observed that the levels of these proteins vary considerably across different cancer cell types, suggesting that treatment responses will differ among patients.
“Our findings will help us better understand the consequences of certain types of chemotherapeutic drugs that are used to treat patients and cause DNA damage,” Buisson adds. “We’ve discovered that the IL-1α and IRAK1 proteins, which play a role in the immune process, vary significantly across different cancer cell types. This suggests that not all patients will react to treatment in the same way.By assessing these protein levels ahead of time, doctors might be able to personalize therapies tailored to individual patients’ needs for improved success rates.”
The research team plans to further investigate this new pathway using mouse models lacking specific factors involved in the process. This next phase of research promises to further refine our understanding of this crucial mechanism and its potential for revolutionizing cancer treatment strategies in the U.S. and beyond.
reference: Bournique E, Sanchez A, Oh S, et al. ATM and IRAK1 orchestrate two distinct mechanisms of NF-κB activation in response to DNA damage. Nat Struct Mol Biol. 2025. doi: 10.1038/s41594-024-01417-0
New Research Sheds light on DNA Damage Response and Cancer Treatment
Researchers at the University of California, Irvine (UCI) have uncovered a previously unknown mechanism by wich cancer cells respond to DNA damage. Published in Nature Structure & Molecular Biology, this discovery could pave the way for more personalized and effective cancer treatments.
World Today News Senior Editor, Sarah Jenkins, discussed these exciting findings with Dr. Jessica Rodriguez, a leading expert in oncology and immunology at Johns Hopkins University.
Sarah Jenkins: Dr. Rodriguez, thank you for joining us today. This new research from UCI seems to offer a notable breakthrough.Could you elaborate on the key findings?
Dr. Jessica rodriguez: It’s my pleasure, Sarah. This research indeed represents a significant advancement in our understanding of how cancer cells react to DNA damage. Traditionally, we’ve focused on the ATM enzyme’s role in this process. However, the UCI team has revealed a wholly new pathway involving the release of a protein called IL-1α, which triggers a cascade of responses culminating in inflammation.
Sarah Jenkins: Can you explain this new pathway in more detail and its implications for cancer treatment?
Dr. Jessica Rodriguez: Certainly. When DNA damage surpasses a cell’s repair capacity, a critical defense mechanism activates, aiming to prevent the damaged cell from potentially becoming cancerous.
This new pathway works differently from the previously known ATM pathway. When DNA damage occurs, the cell releases IL-1α. This protein then travels to neighboring cells, activating the IRAK1 enzyme. This eventually leads to the activation of NF-κB, a key protein complex involved in inflammation and immune response.
Sarah Jenkins: So, this means we have a better understanding of how different types of cancer cells might react to DNA damage. How might this knowledge translate into more effective treatments?
Dr. Jessica Rodriguez: Exactly! The research showed that the levels of IL-1α and IRAK1 vary significantly across different cancer cell types. This strongly suggests that not all patients will respond to DNA-damaging chemotherapies likewise.
By assessing the levels of these proteins in individual patients, doctors could potentially personalize treatment strategies. We could tailor therapies to maximize effectiveness while minimizing side effects, ultimately improving outcomes for patients.
Sarah Jenkins: This is incredibly promising news. What are the next steps for this research?
Dr. Jessica Rodriguez: The UCI team plans to further investigate this new pathway using mouse models by studying what happens when specific factors involved in this process are missing.This will help refine our understanding of the mechanisms at play and pave the way for preclinical trials of new, targeted therapies. It’s an exciting time in cancer research, and this discovery holds immense potential for the future of cancer care.
