BOSTON — Colorectal tumors diagnosed in adults younger than 50 display distinct cellular compositions and gene behaviors that may help explain why the disease can behave aggressively and resist standard treatment, according to a landmark study led by Boston researchers.
The study, published in the journal Nature Medicine, evaluated 189 tumors gathered from patients ranging from their 20s to their 90s, analyzing more than 850,000 individual cells. The cohort included 54 patients diagnosed before age 50, providing the largest comparative cellular dataset to date for early-onset colorectal cancer, according to Dana-Farber Cancer Institute investigators.
Differences in tumor structure
Researchers from the Dana-Farber Cancer Institute, Mass General Brigham, the Broad Institute and the Gene Lay Institute of Immunology and Inflammation discovered that tumors in younger individuals had a markedly higher ratio of connective and supporting cells, known as stromal cells, compared to malignant cells.
Prior research into other solid tumors has linked stromal tissue with resistance to chemotherapy. These supporting cells can generate molecules that hamper immune responses, making it more difficult for a patient’s body to battle malignant growth.
Scientists also identified elevated cellular signaling that helps cancerous cells migrate into nearby tissue. Furthermore, tumors from younger adults exhibited heightened activity of long non-coding RNAs, sometimes called “dark” RNAs, which help regulate gene expression without producing proteins, the research team reported.
“It’s been a bit of a black box,” said Ana Anderson, a senior author of the study and core faculty member at the Gene Lay Institute. “Now we have a research direction. We have a path to follow and hopefully find something that’s really specific to this disease.”
A puzzling and deadly trend
Colorectal cancer has emerged as the leading cause of cancer death among Americans younger than 50, according to the American Cancer Society. Rates among that demographic climbed nearly 3 percent annually between 2013 and 2022. While previous studies have pointed to lifestyle and environmental factors such as diet and ultra-processed foods, scientists have struggled to explain what happens at the cellular level.
The findings offer valuable biological insight to survivors such as Kristen Vincent, who underwent extensive chemotherapy, radiation and surgery after being diagnosed with stage three colorectal cancer at age 37, WCVB and KSL reported.
Next steps for researchers
Outside cancer specialists emphasized that while the findings are promising, immediate clinical breakthroughs remain distant. The study revealed notable biological patterns, but researchers cautioned that the data does not yet prove these cellular mechanisms directly cause more aggressive illness.
Independent experts noted that despite the detailed cellular measurements, the total number of patients examined remains relatively modest. Dr. Christina Annunziata, senior vice president of extramural discovery science at the American Cancer Society, described the findings as an essential initial step toward understanding early development.
Investigators plan to examine how these cellular programs interact with chemicals from diet and gut bacteria to determine whether targeted therapies can be engineered specifically for younger patients.
