Ulcerative Colitis: Targeting p53 Gene for Cancer Prevention
Introduction
A recent study from the Max Delbrück Center and Charité – Universitätsmedizin Berlin, published in Science Advances, reveals that the p53 gene could be critical in preventing the progression of ulcerative colitis (UC) to colon cancer. Led by graduate student Kimberly Hartl at the Berlin Institute for Medical Systems Biology (MDC-BIMSB), this research sheds light on the gene’s role in UC. It opens the door to potential new therapies targeting the early stages of disease progression.
Ulcerative Colitis and Cancer Risk: A Link with the p53 Gene
Ulcerative colitis, an inflammatory disease affecting the colon, is connected to an increased risk of colon cancer. Approximately five million people worldwide suffer from UC, where ongoing inflammation often damages the intestinal lining, specifically the “crypts”—tiny glandular structures that contain stem cells essential for tissue health. In UC patients, these crypt cells stay locked in a “repair mode,” leading to a “regenerative cell state” with excessive stem cell proliferation and a deficiency of mature, functioning cells.
The research points to p53, a well-known tumour suppressor gene, as a key factor in regulating this process. Under normal conditions, p53 helps control cell growth and DNA repair. In patients with a malfunctioning p53 gene, cells remain in this regenerative state, leading to abnormal proliferation and an unhealthy feedback loop that disrupts colon function.
New Diagnostic Possibilities and Treatment Strategies
According to Professor Michael Sigal, a senior researcher of the study, current methods such as colonoscopies allow for the detection of precancerous lesions but are limited in identifying abnormal cells at their earliest stages. The team’s findings suggest the possibility of developing molecular tools for a less invasive diagnostic test, potentially allowing doctors to identify harmful cells earlier—even before visible abnormalities emerge.
Innovative Research Model: The Organoid System
To delve deeper into this repair process, researchers created a 3D organoid model of the colon, grown from mouse stem cells. This mini-organ model allowed them to closely observe cellular behaviour in the absence of functional p53. They discovered that cells without p53 remain in a proliferative state, shifting their metabolism towards rapid glucose consumption—a process called glycolysis. In contrast, active p53 limits glucose metabolism, helping cells revert to a healthy state.
The team tested compounds designed to inhibit glycolysis on these organoids and found that cells lacking p53 were especially sensitive to this treatment. Hartl noted that organoids help scientists pinpoint specific agents that could target these abnormal metabolic pathways, paving the way for therapies to selectively target mutated cells without harming healthy ones.
Future Directions: Clinical Applications and Improved Screening
With these promising findings, the next step involves translating the research to human patients. The team is working on simpler methods to identify cells with defective p53 in colon tissue, with the ultimate goal of clinical trials that could selectively eliminate these cells. Sigal envisions that, once refined, such an approach could potentially reduce the risk of cancer in high-risk UC patients, offering a significant advancement in preventive care.
This study not only underscores the role of p53 in UC but also points towards a future where early detection and targeted therapies could help halt the disease’s progression to cancer, offering new hope for those affected by ulcerative colitis.
Source: Inputs from various media SourcesÂ
Priya Bairagi
I’m a pharmacist with a strong background in health sciences. I hold a BSc from Delhi University and a pharmacy degree from PDM University. I write articles and daily health news while interviewing doctors to bring you the latest insights. In my free time, you’ll find me at the gym or lost in a sci-fi novel.
