A collaborative research team comprising experts from Harvard Medical School, Brigham and Women’s Hospital, Dana-Farber Cancer Institute, and the Broad Institute has conducted a significant analysis of colorectal cancer tumors. This comprehensive study involved examining 189 tumors and revealed a notable finding: younger patients tend to exhibit a higher proportion of connective tissue cells within their tumors. This discovery suggests that such cells may play a role in shielding cancer cells from immune attacks and chemotherapy treatments.
The results of this pivotal research were published on October 29, 2026, in the esteemed journal Nature Medicine.
Since the mid-1990s, there has been a troubling increase in colorectal cancer rates among individuals under the age of 50, in stark contrast to a decline in the same rates among older populations. In the United States, colorectal cancer has become the leading cause of cancer-related deaths in those under 50, with an alarming rise in cases among children and adolescents. Clinical data indicates that early-onset colorectal cancers tend to be more aggressive and respond poorly to treatment, but the underlying reasons for this trend have remained elusive.
Ana Anderson, a co-author of the study, who holds a professorship in neurology at Harvard Medical School and is a core member of the Gene Lay Immunology and Inflammation Research Institute at Brigham and Women’s Hospital, highlighted the paradox faced by younger patients. Despite their generally good health, these individuals often show poor responses to treatment. Anderson remarked that “until now, we have had more questions than answers,” emphasizing that this study represents a fundamental turning point in the understanding of early-onset colorectal cancer.
The research team compared tumors from a diverse age range, spanning from patients as young as 29 years old to those over 90. Out of the 189 tumors analyzed, 54 were from patients under the age of 50, while 135 were from patients aged 50 and older. The substantial sample size enabled the researchers not only to categorize patients into “younger” and “older” groups but also to observe how tumor characteristics evolve with age.
Utilizing cutting-edge single-cell RNA sequencing technology, the researchers analyzed the RNA of each cell within the tumor tissues. RNA, a close relative of DNA, provides insights into which genes are currently active in the cells. One of the advantages of this method is its applicability to frozen specimens stored in biobanks. Through this innovative approach, the team was able to compile a comprehensive cellular atlas of colorectal cancer across different age groups.
The analysis revealed that the proportion of connective tissue cells in younger patients’ tumors relative to malignant cancer cells was significantly higher than that observed in older patients’ tumors. The researchers speculate that these connective tissue cells may secrete compounds that suppress the immune system, thereby allowing tumors to evade immune attacks. Additionally, these cells might physically obstruct chemotherapy drugs from reaching cancer cells, which may partially explain the resistance to treatment observed in younger patients.
Furthermore, the study noted that the cancer cells in younger patients exhibited heightened activity in genes related to intercellular communication. This increased activity may facilitate the mobility of cancer cells. Similar patterns of gene activity have previously been correlated with tumor aggressiveness and metastasis in other cancers.
The research team also identified an abundance of long non-coding RNAs within the tumors of younger patients. These RNAs, which are longer than 200 nucleotides, do not code for proteins, and their functions within the human body and tumors remain largely unclear.
It is important to note that the mechanisms of immune suppression, obstruction of drug efficacy, and promotion of metastasis are currently hypotheses formulated by researchers based on tumor tissue characteristics, and they have yet to be confirmed as direct causes. Moreover, the study does not provide answers as to why early-onset colorectal cancer is becoming increasingly prevalent. To address these questions, Anderson’s team is conducting experiments manipulating these long non-coding RNAs in laboratory settings, aiming to determine whether these molecules contribute to the increased aggressiveness of colorectal cancer in younger individuals and to identify potential new avenues for treatment.