The second leading cause of cancer-related death in men and the third in women, colorectal cancer represents a major public health challenge. Long considered a disease primarily affecting older individuals, its incidence is now increasing among those under 55. This trend has led to a strengthening of prevention and screening programs.
Prevention and Screening: Essential Steps
Most countries have lowered the screening age to 50 to detect the disease earlier. The FIT test, which detects traces of blood in stool samples, is the first step in this process. A positive result does not necessarily indicate the presence of cancer but requires a consultation with a gastroenterologist for a colonoscopy.
Prof. Dr. Elisabeth Letellier, Principal Investigator and Co-Head of the Molecular Disease Mechanisms Group at the University of Luxembourg, explains: “Surgery remains a curative treatment in 90% of cases when cancer is detected early. However, about 20% of patients experience a relapse, leading to progression to more advanced stages, where the prognosis becomes less favorable, particularly in the presence of liver metastases.”
Immunotherapy: A Revolution Underway
Immunotherapy is one of the most significant advances in cancer treatment. Developed through the research of James Allison and Tasuko Honjo—both of whom were awarded the Nobel Prize in Physiology or Medicine in 2018—it works by removing the natural barriers that prevent immune cells from attacking tumor cells. “Checkpoint inhibitors,” a type of targeted antibody, block these inhibitors, allowing immune cells to function more effectively.
However, as Prof. Dr. Elisabeth Letellier points out: “Although this therapy has revolutionized the treatment of many cancers, some remain resistant. This is the case with colorectal cancer, where only a small proportion of patients (5-10%) respond to immunotherapy. So-called ‘cold’ tumors do not attract immune cells, making these treatments ineffective. Research is therefore focused on strategies to ‘warm up’ these tumors by reintroducing immune cells into them.”
Biomarkers: A Valuable Tool for Diagnosis and Treatment
The identification of biomarkers helps refine diagnoses and tailor treatments. There are three types of biomarkers:
• Diagnostic biomarkers: Used to distinguish between a healthy individual and someone with cancer.
• Prognostic biomarkers: Help assess the likely progression of the tumor and the risk of relapse.
• Predictive biomarkers: Indicate whether a patient is likely to respond effectively to a given therapy.
In colorectal cancer, extensive research focuses on biomarkers found in blood and stool samples. The analysis of the gut microbiome, which differs between healthy individuals and cancer patients, could lead to the development of even more precise predictive tests.
Exploring New Therapeutic Solutions: The Microbiome at the Center of Research
Harnessing the gut microbiome is a promising avenue for enhancing treatment effectiveness. The goal is to modify the tumor environment to attract immune cells and improve the success of immunotherapies.
“These therapies can cause side effects and are also very expensive. Therefore, we need to develop ways to make them effective for the majority of patients and identify biomarkers that can predict whether a patient will respond favorably or not.”
Additionally, studies are examining the impact of diet on the microbiome and, by extension, on therapy effectiveness. A clinical trial, conducted in collaboration with the Centre Hospitalier Emile Mayrisch (CHEM), is evaluating how different diets influence responses to immunotherapy.
“The microbiome is still a relatively young but promising field of research. It can act as a second genome through which we are trying to develop new therapies. This is one of the research areas we are working on. The goal is to better understand how the microbiome is regulated and how it can be leveraged for new therapies. At the same time, it is essential to establish dietary recommendations tailored to patients undergoing treatment, as it has been proven that diet plays a key role in modifying the microbiome and could therefore influence the effectiveness of cancer therapies,” concludes Prof. Dr. Elisabeth Letellier.
Towards a Future of Personalized Medicine
Improving prevention and screening, developing biomarkers, and exploring the role of the microbiome are opening new avenues in the fight against colorectal cancer. While many challenges remain, scientific and clinical advances are paving the way for more effective and targeted treatments.
The future lies in personalized medicine, where each patient can benefit from an approach tailored to their biological profile, thereby optimizing their chances of recovery and survival.