liver cancer

Overview

Liver cancer is a malignancy arising in the liver, most commonly referring to hepatocellular carcinoma (HCC), the predominant form of primary liver cancer worldwide; less common primary forms include intrahepatic cholangiocarcinoma, hepatoblastoma, and hepatic angiosarcoma. It is a major cause of cancer-related morbidity and mortality, largely because it is often diagnosed at an advanced stage and frequently develops in the setting of chronic liver disease, including hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, cirrhosis, and metabolic dysfunction-associated steatotic liver disease (MASLD) or metabolic dysfunction-associated steatohepatitis (MASH). The disease is biologically heterogeneous and is shaped by tumor-intrinsic alterations, immune evasion, metabolic reprogramming, angiogenesis, and a complex tumor microenvironment.

From a therapeutic perspective, liver cancer is treated with a combination of surgery, ablation, locoregional therapies such as transarterial chemoembolization, radiotherapy, systemic targeted therapy, and checkpoint inhibitor. In recent years, research has increasingly focused on molecular drivers such as EGFR, AKT/PI3K, mTOR, Nrf2/GPX4, and ferroptosis-related pathways, as well as on biomarkers that may improve prognosis, staging, and treatment selection. Natural compounds, nanomedicine platforms, and combination immunotherapies are also being actively investigated as strategies to overcome resistance to sorafenib, lenvatinib, anti-PD-1 therapy, anti-PD-L1 therapy, atezolizumab, bevacizumab, durvalumab, tremelimumab, and related regimens.

Focus of Latest Publications

Recent publications portray liver cancer, especially HCC, as a highly aggressive and biologically complex malignancy with limited treatment options and substantial recurrence risk. Several studies emphasized that HCC remains a leading cause of cancer-related death worldwide and that unresectable disease, post-ablation relapse, and post-transplant recurrence continue to pose major clinical challenges. Multiple reports also highlighted the growing burden of HCC arising in MASLD/MASH and HBV-associated disease, reinforcing the importance of prevention, surveillance, and risk stratification.

A major theme in the recent literature is the search for molecular targets and biomarkers that explain tumor progression, immune escape, and treatment resistance. Multi-omics and integrative bioinformatics studies identified candidate drivers such as UBE2C, ATIC, CKLF, KCMF1, AARS2, ALDH1A1, TOMM22, PRXL2B, RPRD1A, SETDB2, SMC1A, ATP13A2, and TMEM45B as genes associated with progression, prognosis, immune regulation, or resistance phenotypes. Other studies focused on pathway-level mechanisms, including AKT and ERK signaling, PI3K/AKT/PD-L1, cAMP/PKA, mTOR, EGFR, MET signaling, Nrf2/SLC7A11/GPX4-mediated ferroptosis control, and m6A or m7G RNA modification pathways involving METTL3, METTL1, and IGF2BP1. These findings collectively support the view that liver cancer progression is driven by intertwined metabolic, epigenetic, and immune-regulatory programs.

Immune evasion and the tumor microenvironment were recurring topics. Several studies described immunosuppressive niches shaped by tumor-associated macrophages, exhausted NK cells, T-cell heterogeneity, and altered checkpoint signaling. Investigations of CR1(+) tumor-associated macrophages, CLEC12B-expressing NK cells, and macrophage-related genomic signatures linked these immune states to poor prognosis or therapy response. Other work examined PD-1/PD-L1 axis modulation, including phenethyl isothiocyanate, ST3GAL1, ZNF652, and CD8+ T-cell expansion, as well as the impact of immune checkpoint inhibitors on liver transplantation outcomes and rejection risk. The literature also included studies of vaccine strategies, neoantigen mRNA vaccines, exosome-based antigen delivery, and oncolytic adenovirus or oncolytic virus therapy, reflecting ongoing efforts to improve antitumor immunity in HCC.

Therapeutic innovation was another dominant area. Several studies evaluated combinations involving lenvatinib, sorafenib, atezolizumab plus bevacizumab, durvalumab plus tremelimumab, nivolumab, ipilimumab, camrelizumab, tislelizumab, and anti-PD-1 antibodies in first-line, conversion, neoadjuvant, adjuvant, or salvage settings. Real-world and comparative analyses addressed treatment allocation, response assessment by RECIST 1.1 versus mRECIST, survival dynamics, and outcomes after conversion therapy followed by surgery. Other studies examined locoregional and device-based approaches such as transarterial chemoembolization, microwave ablation, irreversible electroporation, stereotactic body radiotherapy, proton beam therapy, and transarterial radioembolization, often in combination with immunotherapy or targeted agents to improve efficacy and reduce recurrence.

A substantial body of work explored natural products and experimental therapeutics. quercetin, metformin, beta-glucan, asiatic acid, MAP30, sophocarpine derivatives, fenugreek seed extract, curcumin-related strategies, and other phytochemicals were reported to suppress proliferation, promote apoptosis, modulate EGFR or immune signaling, or enhance ferroptosis in HCC models. Nanotechnology-based delivery systems were also prominent, including carrier-free prodrug nanoparticles, lipid nanoparticles, gel-drug systems, exosomes, microspheres, and biomimetic nanoplatforms designed to improve deep tumor penetration, reduce systemic toxicity, and enhance chemoimmunotherapy, photothermal therapy, photodynamic therapy, or cuproptosis induction. These studies often used Huh-7, IR-HepG2 cells, and other human hepatocellular carcinoma cell lines, together with xenograft or orthotopic HCC models, to test antitumor activity.

Diagnostic and prognostic research also advanced. Imaging-based studies used computed tomography scans, elastography, contrast-enhanced ultrasound, and pathomics to identify microvascular invasion, subtype tumors, or predict recurrence. Machine learning algorithms and prognostic models were applied to clinical, radiologic, and molecular data to improve staging, treatment recommendation, and survival prediction, including models for HBV-related HCC and dynamic risk modeling. Additional studies used serum biomarkers, volatile organic compounds, glycoprotein signatures, and noninvasive screening approaches to support earlier detection, which remains critical because many patients are diagnosed late.

Overall, the recent literature presents liver cancer as a disease in which tumor biology, host liver disease, and immune contexture jointly determine outcome. Research is increasingly converging on personalized treatment selection, biomarker-guided risk assessment, and multimodal therapy combining systemic agents, locoregional procedures, and immune-based strategies.

Key Publications

• NEWJun A tumor-resident Staphylococcus epidermidis strain exhibits genomic and metabolic traits driving hepatocellular carcinoma progression. (iScience, 2026, PMID 42256281): "Although bacteria have been detected in hepatocellular carcinoma (HCC), the low microbial biomass has hindered isolation of viable intratumoral strains and evaluation of their functional relevance."
• Jun Evaluation of metabolite biomarker candidates in detecting HCC in patients with liver cirrhosis. (Metabolomics : Official journal of the Metabolomic Society, 2026, PMID 42315713): "Hepatocellular carcinoma (HCC), the most prevalent form of liver cancer, ranks as the third leading cause of mortality globally."
• Jun Integrative multi-omics analysis reveals a gut-liver axis signature of metabolic reprogramming associated with response to transarterial chemoembolization in hepatocellular carcinoma. (BMC gastroenterology, 2026, PMID 42310552): "Transarterial chemoembolization (TACE) is a standard treatment for intermediate-stage hepatocellular carcinoma (HCC), but response is highly variable."
• Jun Piezobiomimetic delivery nanosystem converts cold tumors to hot by parallel PANoptosis/STING activation in hepatocellular carcinoma. (Science advances, 2026, PMID 42308311): "Hepatocellular carcinoma (HCC) remains a challenge for therapeutic efficacy in converting cold tumors into hot ones."
• Jun High-Intensity thermal stress enhances adoptive NK-cell cytotoxicity in poorly differentiated hepatocellular carcinoma. (International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group, 2026, PMID 42311101): "Percutaneous thermal ablation is used to treat early-stage, non-resectable hepatocellular carcinoma (HCC)."
• Jun Development of a bioluminescent enzyme immunoassay for glycocholic acid based on a single-chain variable fragment-nanoluciferase fusion. (Analytical methods : advancing methods and applications, 2026, PMID 42200361): "As glycocholic acid (GCA) has been recognized as a biomarker for hepatocellular carcinoma (HCC), its detection is crucial for the prevention, diagnosis, and treatment of HCC."
• Jun Development of a short-term mouse model of early MASLD for non-invasive pathophysiological tracking via urinary metabolomics and micro-CT. (Life sciences, 2026, PMID 42302927): "Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH), are common chronic liver disorders linked to hepatocellular carcinoma."
• Jun Immune Checkpoint Inhibitor-Induced Rapid Decline in Hepatitis B Virus Markers Improves the Prognosis of Hepatitis B Virus-Related Hepatocellular Carcinoma Patients. (The Journal of infectious diseases, 2026, PMID 41540638): "Limited research exists on immune checkpoint inhibitors (ICIs)' antiviral efficacy in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC)."
• Jun Biomimetic catalase-engineered black phosphorus nanosheets enhance photo-/radio-therapy for hepatocellular carcinoma. (Biomedical materials (Bristol, England), 2026, PMID 42306934): "The hypoxic tumor microenvironment (TME) critically impairs the therapeutic efficacy of photo- and radiotherapy (RT) in hepatocellular carcinoma (HCC)."
• Jun RNF126 is a peroxisomal fate switch enabling redifferentiation therapy in hepatocellular carcinoma. (Proceedings of the National Academy of Sciences of the United States of America, 2026, PMID 42263131): "Tumor hypoxia promotes dedifferentiation and metabolic reprogramming in hepatocellular carcinoma (HCC), undermining normal liver functions."