At #AACR26 plenary, Dr. Ludmil B. Alexandrov @UCSDnews presented a breakthrough mechanistic model for the rise of Early-Onset Colorectal Cancer (EOCRC). 🧬🔬

The hypothesis:
1️⃣ Early-Life pks Activation: Exposure to pks+ gut bacteria (carrying the polyketide synthase island) within the first 5 years of life. 👶🦠
2️⃣ Colibactin Genotoxicity: pks enzymatic activity generates colibactin, imprinting permanent mutational signatures (SBS88/ID18) in normal colon crypts. ✍️💥
3️⃣ Latent Evolution: These "seeded" cells harboring early driver mutations (e.g., APC) undergo multi-decade clonal expansion. ⏳🧫
4️⃣ Phenotype: Overt EOCRC manifests in young adulthood following the accumulation of further damage. 📉

This paradigm shifts our understanding: EOCRC is a long-latency process ignited by early-life microbial triggers. The path forward is targeting pks microbial markers for effective primary prevention! 🎯✨
@OncoAlert @oncodaily @AACR @UCSDHealth @CR_UK @CancerGrand @CD_AACR