Researchers from the Agency for Science, Technology and Research (A*STAR) and the National Cancer Centre Singapore (NCCS) have discovered a crucial link between excessive red meat consumption and an increased risk of colorectal cancer.
Their findings could pave the way for new cancer therapies targeting telomerase, an enzyme involved in the disease's progression.
Colorectal cancer is the third most common cancer worldwide and the second leading cause of cancer-related deaths in Singapore.
While lifestyle choices, particularly diet, are known to influence its development, the precise mechanism connecting high red meat consumption to colorectal cancer risk has remained a mystery. This new study, published in Cancer Discovery, provides the missing piece.
The research team discovered that iron, which is abundant in red meat, reactivates telomerase in cancer cells. Telomerase is an enzyme that maintains the ends of DNA, and when overactive, it helps cancer cells multiply unchecked.
This discovery explains how high intake of red meat can lead to colorectal cancer and provides an opportunity to explore new treatment options.
Potential Breakthrough Treatment
The study did more than just identify the link between iron and telomerase. The researchers also found a potential new treatment strategy using a small molecule called SP2509.
SP2509 works by blocking the interaction between iron and telomerase, preventing the enzyme's reactivation. In lab tests, it not only stopped telomerase activation but also significantly reduced tumor growth, offering a new hope for treating colorectal cancer.
Professor Vinay Tergaonkar, Distinguished Principal Investigator at ASTAR Institute for Molecular and Cell Biology (IMCB), led the multidisciplinary team, which included scientists from ASTAR's Genome Institute of Singapore (GIS), Singapore General Hospital (SGH), and NCCS.
Tergaonkar emphasized the significance of understanding iron's role in cancer progression, stating, "Our future research will focus on refining therapeutic strategies targeting this mechanism, with the hope of developing more effective treatments for patients, especially those with high iron levels."
How the Study Was Conducted
To unravel the connection between iron and colorectal cancer, the team examined samples from colorectal cancer patients and conducted detailed laboratory studies using cancer cell lines.
Collaborating with clinicians from NCCS, they discovered that iron interacts with a protein called Pirin, which senses iron levels. This interaction triggers the reactivation of telomerase in cancer cells, driving their uncontrolled growth.
Further chemical analysis of human colorectal cancer cell lines led the researchers to identify SP2509. This small molecule competes with iron to bind to the protein Pirin, effectively preventing telomerase from being reactivated.
The findings reveal not only a novel way to tackle colorectal cancer but also shed light on how dietary habits contribute to its development.
Broader Implications and Future Research
The discovery is part of a broader national research program called Colo-SCRIPT, which aims to better understand and manage colorectal cancer by exploring the influence of environmental, metabolic, and microbial factors.
Associate Professor Iain Tan, Senior Consultant in the Division of Medical Oncology at NCCS, explained the importance of this ongoing research. "Through Colo-SCRIPT, we will continue to investigate the role of iron and other risk factors in driving colorectal cancer.
Our findings offer valuable insights into how different subtypes of the disease develop and can help us identify new methods to prevent and treat it," Tan said.
The study's findings are promising, as they provide a clearer understanding of how high iron levels from red meat may contribute to cancer and point to potential new treatment options.
By blocking the interaction between iron and telomerase, therapies like SP2509 could become vital tools in combating colorectal cancer, especially in patients with diets high in iron-rich foods.
While these results are encouraging, the researchers plan to refine their therapeutic strategies and explore additional small molecules that might target this newly identified pathway.
As Professor Tergaonkar noted, "We are excited about the potential of small molecules like SP2509 to revolutionize cancer care and improve outcomes for patients globally."
In summary, the research reveals a direct connection between red meat consumption and colorectal cancer, driven by iron's activation of telomerase.
This discovery not only helps explain why red meat increases cancer risk but also opens the door to new treatments aimed at blocking this harmful pathway. With continued research, these findings could lead to more effective therapies and preventative strategies against colorectal cancer.
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