Patients whose livers are fatty are significantly more likely to develop the most aggressive kind of bowel cancer spread, researchers at VIB and KU Leuven in Belgium report in Nature. They have also worked out how.
Colorectal cancer accounts for nearly 1 in 10 cancer diagnoses and is now the leading cause of cancer death in people under 50, according to the researchers. Up to half of patients develop secondary tumors in distant organs, mostly the liver, and that is what drags survival down.
Not all liver metastases behave alike. Where the tumor stays walled off from healthy liver tissue, five-year survival reaches about 73%. Where cancer cells infiltrate and mingle with healthy tissue, in what are called replacement metastases, survival falls below 44%. Until now, the team says, little was known about what produces the aggressive kind, and no therapy targets it.
Fat as fuel
The study, led by Prof. Sarah-Maria Fendt of the VIB-KU Leuven Center for Cancer Biology, compared patient samples with experimental models. Patients with fat in the liver, known as steatosis, were significantly more likely to develop replacement metastases.
The mechanism runs through a chain of steps. In a fatty liver, high levels of fatty acids stabilize MYC, a protein known to drive cancer growth. Stable MYC raises production of proline, an amino acid that is a building block of collagen. The collagen forms a scaffold that lets tumor cells push into the liver and spread.
“This work shows that a condition we typically consider a background metabolic issue can directly shape how cancer behaves,” said Fendt, the senior author. In plainer terms, she said, “the fatty liver provides both the signal and the construction materials that tumors need to grow more aggressively.”
What it could change
The nearest practical use is in clinical trials. Drugs aimed at MYC are already being tested in patients for safety, and the study suggests they may work best in people with fatty liver and replacement metastases. Picking patients that way, Fendt said, could make trials more efficient.
In advanced experimental systems, including patient-derived tissue models, the team cut the formation and growth of aggressive metastases by targeting MYC, proline production or collagen formation. Liver fat content could also serve as a biomarker to guide treatment and predict how the disease progresses, according to the researchers.
First author Dr. Yiming Peng-Winkler, of VIB-KU Leuven and University Hospital Dusseldorf, said treating cancer means looking at the environment the tumor depends on, and not only at the tumor.
VIB’s own release carries a caution: a breakthrough in research is not a breakthrough in medicine, and the path to new therapies takes years. People worried about fatty liver or bowel cancer should speak to their doctor.
Sources
- Fatty liver drives a more dangerous form of cancer spread
- Fatty liver disease fuels aggressive metastatic colorectal cancer spread
- Fatty liver drives a more dangerous form of cancer spread
