Medicine shifts overnight.
15% of CRCs are dMMR.
Surgery was standard—until now.
Diaz, Cercek @mskcancercenter.bsky.social @nejm.org: dostarlimab = 82% CR, 92% RFS, low toxicity.
Immunotherapy first. Surgery backup.
Paper: nejm.org/doi/full/10.1056/NEJMoa2404512
#Lynch #CRC #Immunotherapy
Hear directly from lead author Ludmil B. Alexandrov: lnkd.in/ekg6yKeJ
#EOCRC #Never2Young #ColorectalCancer #Microbiome #GutHealth
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TAKE-HOME 2: Emerging solutions include microbiome diagnostics and therapies targeting these bacteria (faecal metagenomic sequencing, diet, probiotics, bacteriophages, vaccines).
Until EOCRC risk is better understood and managed, we should advocate lowering the screening age to 40.
TAKE-HOME 1: Childhood colonisation by colibactin-producing bacteria may fundamentally alter lifelong colorectal cancer risk, particularly for early-onset cases.
Detection of these specific mutational signatures in normal mucosa could enable early risk stratification.
FUTURE RESEARCH NEEDED: Adolescent microbiome analyses linking bacterial colonization with later cancer risk
Animal models testing preventive strategies
Identifying other mutagens contributing to early-onset cases.
KEY FINDING: These signatures appeared without active bacterial colonization, suggesting early-life exposure creates DNA "scarring" that increases lifelong cancer risk.
The mutations affected critical colorectal cancer driver genes.
NEW DISCOVERY: UC San Diego researchers sequenced 802 colorectal cancer cases, finding colibactin-associated signatures were significantly higher in patients diagnosed <50 years of age.
Younger patients showed more colibactin-induced mutations.
BACKGROUND: Colibactin is a genotoxin produced by certain E. coli bacteria that introduces distinct DNA mutations.
Previous studies validated colibactin's role in creating detectable genomic "mutational signatures" (SBS88 and ID18).
STATS: Millennials (born ~1990) have a 2.4× higher risk of colon cancer and 4.3× higher risk of rectal cancer compared to Baby Boomers (born ~1950).
But why is this happening?
THE ISSUE: As a gastroenterology trainee 20 years ago, early-onset colorectal cancer cases were rare and mostly familial.
Now, diagnoses in young, healthy patients without family histories are unnervingly common.
COOLEST THING IN MICROBIAL MEDICINE THIS WEEK 🔬🧫
New research in Nature suggests early-onset colorectal cancer (EOCRC) might be increasing due to childhood colonisation by colibactin-producing bacteria.
A thread on this fascinating discovery... 🧵
#MicrobialMedicine
“Back then, the overwhelming public sentiment was: never again. Today, it seems: never what?”—Siddhartha Mukherjee
Exceptional essay
Gift link
www.nytimes.com/2025/03/10/o...
