Genetic Factors Drive Metastasis Formation in Colorectal Cancer

Colorectal cancer remains one of the leading causes of cancer-related deaths worldwide, responsible for approximately 10% of all cancer fatalities. Its threat escalates significantly when the cancer spreads beyond the original site, forming metastases primarily in the liver and lungs, and less frequently in the brain. A recent study led by Dr. Björn Sander, a pathologist at Hannover Medical School (MHH), has provided new insights into the genetic mechanisms underlying metastasis development in colorectal cancer.

The research focused on the role of chromosomal alterations—changes in the structure and number of chromosomes—in influencing the propensity of cancer cells to metastasize. The team analyzed over 3,800 cases of colorectal cancer and discovered that metastases to the brain exhibit a higher frequency of genetic mutations and chromosomal changes compared to liver and lung metastases. These findings suggest that different genetic alterations may guide the tumor cells to specific organs.

A critical element in this process involves the KRAS gene, which encodes a protein essential for cellular signaling controlling growth and division. Mutations and duplications of the KRAS gene are particularly common in brain metastases, providing the tumor cells with advantages needed to colonize the brain environment. Notably, the brain's high oxygen demand and the presence of the blood-brain barrier pose unique challenges for metastatic cells. Tumor cells with KRAS mutations appear better equipped to adapt to the oxygen-limited and protective conditions in the brain.

The study also indicates that the genetic patterns seen in brain metastases tend to develop later in the course of tumor progression, contrasting with the more immediate genetic changes observed in liver and lung metastases. This temporal difference implies that the genetic evolution of cancer cells influences their organ-specific spread.

Understanding these genetic changes offers promising avenues for personalized therapies. Targeting chromosomal instability or specific gene mutations like KRAS could weaken metastatic tumor cells and improve treatment responses. Dr. Sander emphasizes that these insights might eventually lead to tailored treatment strategies, aiming to detect and intervene in metastasis formation at earlier stages.

The research, published in Nature Communications, enhances our understanding of the molecular processes driving cancer dissemination. As the quest for more effective treatments continues, uncovering the genetic signatures associated with metastasis may pave the way for novel therapeutic approaches, potentially reducing mortality from advanced colorectal cancer.

Source: https://medicalxpress.com/news/2025-06-genetic-metastasis-formation-colorectal-cancer.html