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Dan Worthley

@danworthley.bsky.social
23 followers 39 following 11 posts

Gastroenterologist @ Colonoscopy Clinic | Cancer scientist | Dad & husband | Enthusiastic (but appalling) runner | MBBS (Hons), PhD, MPH, FRACP, AGAF |

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Dan Worthley @danworthley.bsky.social · 27/04/2025
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
nejm.org
Nonoperative Management of Mismatch Repair–Deficient Tumors | NEJM
Among patients with mismatch repair–deficient (dMMR), locally advanced rectal cancer, neoadjuvant checkpoint blockade eliminated the need for surgery in a high proportion of patients. Whether this ...
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Dan Worthley @danworthley.bsky.social · 26/04/2025
Hear directly from lead author Ludmil B. Alexandrov: lnkd.in/ekg6yKeJ #EOCRC #Never2Young #ColorectalCancer #Microbiome #GutHealth Please follow for the Coolest Thing in Microbial Medicine each week!
lnkd.in
You know the recent spike in colorectal cancer in people under 50…what’s… | Albert "Al" P. Pisano, Ph.D.
You know the recent spike in colorectal cancer in people under 50…what’s the cause? There are new insights in a Nature paper out today. The paper discusses mutations to colon cells early in life that ...
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Dan Worthley @danworthley.bsky.social · 26/04/2025
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.
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Dan Worthley @danworthley.bsky.social · 26/04/2025
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.
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Dan Worthley @danworthley.bsky.social · 26/04/2025
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.
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Dan Worthley @danworthley.bsky.social · 26/04/2025
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.
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Dan Worthley @danworthley.bsky.social · 26/04/2025
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.
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Dan Worthley @danworthley.bsky.social · 26/04/2025
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).
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Dan Worthley @danworthley.bsky.social · 26/04/2025
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?
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Dan Worthley @danworthley.bsky.social · 26/04/2025
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.
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Dan Worthley @danworthley.bsky.social · 26/04/2025
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
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Reposted by Dan Worthley
Eric Topol @erictopol.bsky.social · 16/03/2025
“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...
nytimes.com
Opinion | Covid’s Deadliest Effect Took Five Years to Appear (Gift Article)
What once belonged to all of us now belongs to corporations.
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