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Extensive and differential platinum chemotherapy mutagenesis in livers of children | Science
Duplex sequencing (NanoSeq) of normal liver tissue from childhood cancer survivors revealed extensive and highly differential mutagenesis caused by platinum-based chemotherapy, providing a direct molecular link between treatment exposure and late adverse effects. The study found that platinum agents leave a distinctive mutational signature in pediatric hepatocytes that differs markedly from age-re…
Complete Regression of Hepatoblastoma after Interleukin-15– and Interleukin-21–Coexpressing CAR T-Cell Therapy
A patient with hepatoblastoma achieved complete regression following treatment with CAR T cells engineered to coexpress interleukin-15 and interleukin-21, as reported in a brief communication in the New England Journal of Medicine. The dual-cytokine CAR-T construct represents a novel approach to enhancing T-cell persistence and antitumor activity in a pediatric solid tumor that has limited options…
Phase 3 TALENTop trial: liver resection after atezolizumab and bevacizumab lengthens time to treatment failure in locally advanced hepatocellular carcinoma
In the randomised phase 3 TALENTop trial (24 hospitals in China), 201 patients with hepatocellular carcinoma and macrovascular invasion who had responded to induction atezolizumab plus bevacizumab were randomly assigned to liver resection followed by maintenance treatment or to maintenance treatment alone. Median time to treatment failure was 20.4 months in the surgery group versus 11.8 months in …
Alcohol-attributable cancer deaths in the USA doubled between 1990 and 2023
Cancer deaths attributable to alcohol in the USA rose from 11,361 in 1990 to 23,126 in 2023 — a doubling over 33 years. The figures come from a secondary analysis of Global Burden of Disease data, so they are attributable-fraction estimates rather than counted deaths: they describe the scale of the problem in a population, not the risk faced by any one person. Increases spanned liver, breast, colo…
Pemigatinib improves progression-free survival but not overall survival in first-line FGFR2-rearranged cholangiocarcinoma (phase 3 FIGHT-302)
In the randomized phase 3 FIGHT-302 trial, first-line pemigatinib extended median progression-free survival to 8.3 months versus 6.8 months with gemcitabine-cisplatin chemotherapy in advanced cholangiocarcinoma harbouring an FGFR2 rearrangement (HR 0.58; 95% CI 0.39-0.87; p=0.0078). Objective response rate was 47% versus 15% and median duration of response 14.2 versus 6.3 months. Overall survival …
Molecular mechanisms and pathogenesis of MASH
A comprehensive Nature Review synthesizes current knowledge of the molecular and cellular mechanisms driving metabolic dysfunction-associated steatohepatitis (MASH) and its progression to hepatocellular carcinoma (HCC). The article maps key pathogenic pathways — including lipotoxicity, inflammation, and fibrosis — that underlie the MASH-to-HCC transition. As MASH is becoming the fastest-growing et…
Efficacy and Tolerability of Zenocutuzumab in Advanced NRG1 Fusion-Positive Biliary Tract Cancer
Zenocutuzumab, a HER2xHER3 bispecific antibody, produced responses in 7 of 19 evaluable patients with advanced NRG1 fusion-positive cholangiocarcinoma — an overall response rate of 36.8% (95% CI 16.3-61.6) in the single-arm phase 2 eNRGy trial. Median duration of response was 7.4 months and median progression-free survival was 9.2 months (95% CI 3.9-11.1). Most treatment-related adverse events wer…
Liver resection after atezolizumab and bevacizumab versus maintenance therapy for locally advanced hepatocellular carcinoma (TALENTOP): a multicentre, open-label, randomised, phase 3 trial
In the randomised phase 3 TALENTOP trial (24 hospitals in China), patients with hepatocellular carcinoma and macrovascular invasion first received atezolizumab plus bevacizumab; 201 were then randomly assigned to liver resection (n=101) or continued systemic therapy (n=100). Median time to treatment failure was 20.4 months after surgery versus 11.8 months with maintenance therapy (HR 0.60; 95% CI …
Durvalumab and tremelimumab, with or without lenvatinib, combined with transarterial chemoembolisation in participants with embolisation-eligible hepatocellular carcinoma (EMERALD-3): a global, randomised, open-label, sponsor-blinded, phase 3 study
Adding immunotherapy (durvalumab plus tremelimumab) and lenvatinib to transarterial chemoembolisation prolonged progression-free survival but NOT overall survival. In the phase 3 EMERALD-3 trial (n=760, embolisation-eligible hepatocellular carcinoma), median progression-free survival was 13.0 versus 9.8 months with chemoembolisation alone (HR 0.70; 95% CI 0.57-0.86; p=0.0007), while median overall…
Spatial multi-omics landscape of colorectal cancer macro- and micrometastases
Integrated spatial transcriptomic, genomic, and proteomic profiling of colorectal cancer metastases reveals early clonal divergence, stem-like cellular features, and immunosuppressive microenvironments characterized by T cell exhaustion already present at the micrometastasis stage. The study identifies a colorectal liver micrometastasis-specific six-gene signature (CLiMi) that correlates with mini…