Antioxidant NAC reduces precancerous lesions (by Radyk et al via Nat Metab)NADPH-producing enzymes act as a critical barrier against pancreatic precancer formation. Using KrasG12D-driven mouse acinar cells, Radyk and colleagues performed temporal metabolic and transcriptomic profiling during acinar-to-ductal metaplasia (ADM), an early reversible stage of pancreatic tumorigenesis. They observed global changes in central carbon metabolism and identified strong induction of NRF2-targeted genes during ADM formation, particularly those coding for NADPH-generating enzymes such as glucose-6-phosphate dehydrogenase (G6PD) and malic enzyme-1 (ME1). Deficiency of G6PD or loss of Me1 in mouse models increased oxidative stress and lipid peroxidation and accelerated the formation of ADM and pancreatic intraepithelial neoplasia (PanIN) lesions. These effects were attenuated by pharmacological antioxidant treatment in vivo and ex vivo. Conversely, depletion of the antioxidant glutathione promoted precancerous lesions in both primary human acinar cells and mice. Notably, Me1 loss, but not G6PD deficiency, promoted faster progression to pancreatic ductal adenocarcinoma, revealing distinct stage-specific metabolic requirements. These findings suggest redox-regulating metabolism is a key determinant of pancreatic cancer initiation, however, additional studies are needed to better understand precancer metabolic changes before translation to humans.Radyk MD, … Lyssiotis CA. Nat Metab. 2026 Apr;8(4):824–839.Two evolutionary scenarios of early hepatocarcinogenesis (by Zhang et al via Cancer Cell)A recent study suggested two evolutionary scenarios of early hepatocarcinogenesis. By screening 44,714 human liver specimens, Zhang and colleagues identified 21 very early hepatocellular carcinomas (veHCCs) arising within 17 cancer-prone dysplastic nodules (DNs) and performed integrated whole-genome, transcriptomic, immune, and spatial profiling of paired premalignant and malignant lesions. The researchers found that TERT alterations were present in 82% of cancer-prone DNs, indicating a predisposing rather than causative role in malignant transition. In addition, accumulation of copy number alterations (CNAs) rather than single-nucleotide variants was strongly associated with the transition to malignancy. Immune analyses revealed that cancer-prone DNs were largely immune-inactive, challenging the paradigm that hepatocellular carcinoma (HCC) initiation requires chronic inflammation. Notably, 43% of veHCCs displayed an inflamed but immune-evasive phenotype. These findings indicate that early HCC develops through either CNA-dominant progression or inflamed progression with early immune evasion, highlighting opportunities for early detection and immunotherapeutic intervention.Zhang Z, … Hui L. Cancer Cell. 2026 Mar 26:S1535-6108(26)00157-1.Electronic health record (by Lunasora05via Wikimedia Commons)A simple electronic health record (EHR)–based model accurately identifies individuals at elevated risk of pancreatic ductal adenocarcinoma (PDAC) years before diagnosis. Using a longitudinal, deidentified US EHR and claims database comprising more than 11 million adults across 54 US health systems, Mavromatis and colleagues developed and validated the PDAC Risk Model for Earlier Detection (PRIME), which was further validated internationally in the UK Biobank cohort. The model incorporated 19 demographic, clinical, and laboratory variables, including age, sex, blood type, smoking status, and history of pancreatitis, diabetes, gastrointestinal conditions, abnormal liver enzymes, and prior cancers. PRIME demonstrated good discrimination and calibration, with an area under the curve (AUC) of approximately 0.75 for 36-month pancreatic cancer risk in US cohorts and 0.71 in the UK Biobank cohort. Individuals in the top 1% risk percentile had a significantly increased risk of PDAC (HR, 7.63; 95% CI, 6.85–8.49) compared with those at average risk. The findings show that an interpretable and generalizable model based on routinely available clinical data can effectively stratify pancreatic cancer risk across diverse patient populations, providing a practical foundation for targeted surveillance, biomarker testing, and early detection strategies.Mavromatis LA, … Grams ME. JAMA Oncol. 2026 Mar 26:e260372.Lung cancer (by Naturopathic Doctor News and Review via Flickr)Implementation of England’s national lung cancer screening program substantially increased early-stage lung cancer detection while demonstrating feasibility and equity at population scale. Lee and colleagues evaluated the progress and outcomes of the NHS England Lung Cancer Screening Programme from its launch in 2019 through March 2025. The program invited more than 2.5 million individuals aged 55 to 74, completed approximately 1.2 million lung health checks (LHCs, 83.2% delivered by phone), conducted more than 528,000 low-dose computed tomography (LDCT) scans for individuals meeting a specific risk threshold, and diagnosed 7,193 lung cancers. Among identified cases, 75.7% were diagnosed at an early stage, including 63.1% at stage 1 and 12.6% at stage 2, substantially improving early-stage detection rates in England, particularly in socioeconomically deprived regions. Although the program successfully reached high-risk populations, participants from non-White ethnic groups, those in the most deprived areas, and women were less likely to attend invited LHCs or follow-up LDCT scans. These results provide strong evidence that risk-targeted lung cancer screening can be successfully implemented nationwide, improving early detection and informing international screening policies.Lee RW, … Baldwin DR; UK Lung Cancer Screening Research Consortium. Nat Med. 2026 Mar 23.
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