The study examine the early emergence of metastatic potential in colorectal cancer, specifically focusing on the oncofetal cell states that appear at the invasive front of stage T1 tumors. Through spatial transcriptomics and the creation of a multiregional organoid biobank, researchers discovered that these high-risk cellular programs are ubiquitous even in non-metastatic early cancers. The study demonstrates that metastatic competence is not driven by new genetic mutations at the tumor’s edge, as cells in the core and the front remain genetically similar. Instead, the transition to an invasive state is triggered by the tumor microenvironment, where specific cancer-associated fibroblasts mimicking normal submucosal trophocytes induce plastic changes in the cancer cells. Ultimately, the research suggests that while these aggressive phenotypes appear early, successful metastasis requires additional hurdles like immune evasion.

References:

• Buissant des Amorie J R, Hageman J H, Brunner S R, et al. Emergence of oncofetal plasticity is ubiquitous in early colorectal cancers[J]. Nature, 2026: 1-11.