Editors’ Selections from Relevant Scientific Publications

The intestinal epithelium showing crypts (by STEMCELL Technologies Inc via Wikimedia Commons)Crypt density and epigenetic changes are important in intestinal tumourigenesis driven by Apc mutations, the most common initiating event in conventional adenomas that activates Wnt signaling. Gaynor and colleagues engineered two mouse models with inducible Apc deletion in intestinal stem cells (ISCs) arising from either self-renewal or dedifferentiation. They found that Apc deletion only drove tumor formation when mutant intestinal crypts were in close proximity, regardless of ISC source. Additionally, they discovered that thousands of enhancer elements became more accessible in adenoma-resident Apc-null ISCs, activating additional oncogenes. The authors conclude that Apc mutations trigger adenomas only when Wnt-activated crypts reach a “critical mass” accompanied by altered chromatin accessibility at thousands of enhancers. These findings provide new insight into the early steps of intestinal tumor initiation.Gaynor L, … Shivdasani RA. Nature. 2025 Jan 8.Trim28+/D9 effects on early-life epigenomes (by Panzeri et al. via Nat Cancer)Cancer risk is not merely a matter of mutations—a new study shows that genomic DNA methylation patterns established early in life also affect the odds of tumorigenesis. Panzeri and colleagues analyzed a mouse model with only one functional copy of the Trim28 gene, which encodes a master regulator of epigenetic modification during development. These animals exhibited divergent patterns of epigenetic modification as early as 10 days of age that gave rise to two distinct body types—normal weight and obese—that also exhibited different levels of cancer risk. “Light” mice developed aggressive tumors at multiple sites and proved more susceptible to death from cancer relative to “heavy” mice, with DNA methylation patterns strongly associated with reduced silencing of known oncogenes. These results suggest the opportunity to identify congenital “high cancer risk” epigenetic signatures in humans that could guide cancer screening and treatment.Panzeri I, … Pospisilik JA. Nat Cancer.2025 Jan 24.The 10-feature multi-omic cross-biofluid biomarker panel (by Kane et al. via Sci Rep.)Pancreatic cancer is challenging to detect early, and patient prognosis remains poor, with a 5-year survival rate of 13%. “Liquid biopsy” tests for tumor-specific biomarkers could enable earlier intervention, and Kane and colleagues performed multi-omic analyses of biofluids from 32 subjects to develop a tool for cancer risk assessment. They analyzed protein and RNA from both serum and pancreatic cyst fluid (PCF), identifying biomarker combinations in each that were specifically associated with high cancer risk. The most effective test combined a 4-feature PCF panel and a 6-feature serum panel, comprising seven proteins and three miRNAs. The 10-feature cross-biofluid multi-omic biomarker panel achieved an area under the ROC curve of 0.97, with a sensitivity of 91.7% and a specificity of 90.9%. Pending further validation, these biomarkers could offer valuable insights into pancreatic cancer risk, helping doctors identify patients with pancreatic cystic lesions who require most intensive monitoring.Kane LE, … Maher SG. Sci Rep.2025 Jan 2;15(1):129.Quit smoking sign (from NARA & DVIDS Public Domain Archive)People are more likely to stop smoking if they undergo an integrated counselling and pharmacotherapy program than by calling a quitline (QL). Cinciripini and colleagues recruited 630 current smokers from a lung-cancer screening program and randomized them into three groups (n = 210/group). The QL group received phone counselling and nicotine replacement therapy, the “QL+” group also received medication management from screening clinicians, and the “integrated care” (IC) group had counselling and medication management by tobacco treatment specialists. After 6 months, 32.4% of the IC group reported abstinence, compared to 27.5% in the QL+ group and 20.5% in the QL group, though the difference between IC and QL+ was not statistically significant. The results suggest that intensive counselling and medication support offer the best cessation strategy, while QL+ may be a viable option in low-resource settings.Cinciripini PM, … Robinson JD. JAMA Intern Med.2025 Jan 13.