Researchers at Oxford University have made a startling discovery that could revolutionize cancer treatment. Their study, recently published in the journal Nature Genetics, revealed the surprising impact of persistent inflammation on cancer development in blood stem cells with p53 mutations, known as the “guardian of the genome”.
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Impact of TP53 mutations on cancer development
The p53 protein, generated by the TP53 gene, is essential in preventing cancer by triggering apoptosis, a process by which cells “self-destruct” to prevent the proliferation of damaged cells. However, genetic mutations can cause the p53 protein to become ineffective, allowing damaged cells to divide uncontrollably and contribute to the development of cancer.
Up to 50-60% of human cancers involve mutations in the TP53 gene, and haematopoietic stem cells (HSCs) with such mutations are associated with acute myeloid leukemia (AML), a serious form of blood cancer.
The study investigated the effect of chronic inflammation on cancer progression. The research team used a technique called TARGET-seq to investigate the effects of TP53 mutations on cancer progression.
The results showed that TP53 cells with mutations had significantly higher activation of inflammation-related genes. Moreover, these cells multiplied more rapidly when exposed to inflammatory stimuli compared to healthy HSCs. Mutated CSHs were also found to produce fewer white blood cells and were more “resistant” to inflammation-induced cell death.
New perspectives for the treatment of leukemia
Researcher Alba Rodriguez-Meira, co-author of the study, pointed out that these findings open new perspectives in understanding how genetic defects and inflammation contribute to the development of cancer. This research could also lead to the development of innovative therapeutic approaches to treat leukemia with TP53 mutations and other cancers.
The study’s lead author, Adam Mead, emphasized that the link between inflammation and genetic evolution in cancer has broad implications, and that the challenge is to identify ways to intervene to more effectively treat or prevent inflammation associated with cancer progression.
This promising discovery could represent an important step in this direction and could have a significant impact on future cancer treatment modalities.
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