DNA discovery provides major boost in fight against aggressive cancers
[July 9, 2023: Staff Writer, The Brighter Side of News]
Researchers have shed new light on the fundamental genetic structure that propels the aggressive spread of colorectal or bowel cancer. (CREDIT: Creative Commons)
In an era where the battle against cancer continues to dominate global healthcare concerns, a pivotal breakthrough in the field of cancer research has emerged from the corridors of the University of Otago, New Zealand.
Led by the dedicated team of Associate Professor Aniruddha Chatterjee, Dr Euan Rodger, and Dr Rachel Purcell, the researchers have shed new light on the fundamental genetic structure that propels the aggressive spread of colorectal or bowel cancer - a disease that currently ranks as the second highest cause of cancer death in Aotearoa.
Published in the Cell Press journal iScience, their pivotal study heralds a significant stride towards the detection, prevention, and ultimately, the cure for tumors notorious for their rapid growth and metastatic prowess. It is metastasis, the process of cancer cells breaking away from the primary tumor and spreading to distant organs, that is predominantly responsible for cancer-related fatalities.
"Despite this profound impact, how tumors become metastatic and so deadly, and what is different about these tumor cells remains largely unknown. The DNA instructions – the blueprint of a cell - and how and where these instructions go wrong in cancer cells provide important clues in understanding why this happens,” says Dr Rodger.
At the core of the research lies the study of DNA methylation – a chemical process that modifies the DNA in a cell, regulating its behaviour. This 'epigenetic code', as it's commonly referred to, holds a tremendous potential to unlock the mysteries of metastasis and apply this knowledge for the benefit of patients suffering from the deadly progression of the disease.
The dedicated team delved into the DNA methylation map and the behavior of the DNA within bowel cancer patients. In a meticulous and systematic approach, the team studied clinical samples from 20 patients. Each of these samples came from two sources – the primary tumor in the colon and the tumors that had managed to break free and metastasize to the liver.
The results of this comprehensive investigation were striking and enlightening. "We have discovered almost 300 gene regions that show distinct DNA methylation levels in liver metastasis," reveals Dr Rodger. "These changes are unique to aggressive liver metastasis and are not present in primary tumors or in normal colon. The genes that have the unique methylation signature have important functions in cells."
Graphical abstract: An epigenetic signature of advanced colorectal cancer metastasis. (CREDIT: iScience)
Their discovery has profound implications for our understanding of the biology of cancer, suggesting that these unique methylation patterns may be the key that allows cancer cells to become so aggressive and invasive. This new knowledge could prove to be an instrumental tool in crafting more effective strategies for battling colorectal cancer.
Associate Professor Chatterjee stresses the significance of the discovery, particularly in the New Zealand context, where every year, 1,200 lives are lost to bowel cancer. "Patients with distant metastases, such as liver metastasis as we have studied in this work, unfortunately have very low five-year survival rates," he explains.
Global differences in DNA methylation between normal colon, primary colorectal cancers and liver metastases. (CREDIT: iScience)
The study also casts a sharp focus on certain demographic groups. The occurrence of colorectal cancer has alarmingly been on the rise in people under 50 years old, and it is spreading in Māori and Pasifika populations at a disproportionately higher rate. It is also noteworthy that Māori and Pasifika are more likely to present directly to emergency departments with advanced colorectal tumors.
But the research conducted by Chatterjee, Rodger, and Purcell is not merely an exposition of grim facts. It is a beacon of hope. "Our work will open new avenues for understanding why cancer cells become so aggressive and will lead to better outcome prediction and new targets to treat these tumors in the future," shares Associate Professor Chatterjee.
Differential methylation patterns between normal colon, primary colorectal cancers and liver metastases. (CREDIT: iScience)
Equipped with the support of the Health Research Council and the Royal Society of New Zealand Te Apārangi Marsden Fund, Chatterjee and Rodger are set to undertake more extensive research on metastatic cancers.
This newly garnered support propels the team to unravel further mysteries, strengthen our understanding, and inch us ever closer to mitigating, and ultimately defeating, the colossal challenge posed by colorectal cancer.
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