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Plasma GPC3 reflects tumor GPC3 expression and predicts clinical outcomes in advanced HCC treated with atezolizumab + bevacizumab - PubMed
2 months ago
- Plasma GPC3 levels correlate with tumor GPC3 expression in hepatocellular carcinoma (HCC).
- High plasma GPC3 (>10 pg/ml) is associated with worse clinical outcomes, including shorter progression-free and overall survival.
- Plasma GPC3 was a better predictor of 6- and 12-month outcomes compared to tumor-based measures.
- The study suggests plasma GPC3 as a non-invasive biomarker for HCC, particularly in patients treated with atezolizumab plus bevacizumab.
- Discrepancies between plasma and tumor GPC3 levels were noted, indicating potential complementary roles in assessment.
Multi-omics profiling reveals cholic acid-mediated immunosuppression driven by peritumoral ductular reactions in hepatocellular carcinoma - PubMed
2 months ago
- Multi-omics profiling reveals cholic acid-mediated immunosuppression in hepatocellular carcinoma (HCC).
- Peritumoral ductular reactions predict poor clinical outcomes and correlate with cirrhosis severity.
- Three distinct cholangiocyte subpopulations identified, with Small_duct_type_Cho promoting stromal remodeling.
- Cholic acid enrichment at tumor margins induces CD8+ T cell dysfunction via NR1H4-dependent PD1 upregulation.
- NR1H4 inhibition synergizes with anti-PD1 therapy, significantly suppressing tumor growth in murine models.
- Ductular reactions serve as both a prognostic biomarker and therapeutic target in HCC.
Transcriptional factor ZMYM3 promotes hepatocellular carcinoma metastasis by upregulating CTTN and inducing invadopodia formation - PubMed
2 months ago
- ZMYM3 is upregulated in hepatocellular carcinoma (HCC) tissues and linked to poor prognosis.
- ZMYM3 enhances HCC cell proliferation, invasion, and metastasis.
- ZMYM3 promotes invadopodia formation and epithelial-mesenchymal transition (EMT) in HCC cells.
- ZMYM3 directly binds to the CTTN promoter, increasing its expression and enhancing metastasis.
- ZMYM3 overexpression predicts high recurrence risk and poor prognosis in HCC patients.
Asynchronous Transitions from High-Risk Hepatoblastoma to Carcinoma - PubMed
2 months ago
- Pediatric hepatocellular tumors include hepatoblastoma (HB) and hepatocellular carcinoma (HCC), with some showing mixed features (HBCs).
- HBCs consist of heterogeneous mixtures of HB-like, HBC-like, and HCC-like molecular cell types.
- HBC outcomes are worse than HB, with HBC cells being more chemoresistant due to cell identity, genetic alterations, and embryonic differentiation stage.
- HBC cells originate from HB cells arrested at early hepatic stem cell development stages due to aberrant WNT signaling activation.
- Inhibition of WNT signaling promoted differentiation and enhanced chemotherapy sensitivity.
- HBCs reflect dynamic processes of multiple HB-to-HBC and HBC-to-HCC transitions, indicating evolutionary complexity.
- A study limitation is the inability to pinpoint chemotherapy-induced genome modifications' role.
A Phase 1b Study of Lenvatinib plus Nivolumab in Patients with Unresectable Hepatocellular Carcinoma - PubMed
2 months ago
- Phase 1b study evaluates lenvatinib + nivolumab in unresectable hepatocellular carcinoma (uHCC).
- Study conducted in Japan with adults (≥20 years) with confirmed HCC.
- Patients received lenvatinib (8 mg or 12 mg daily) + nivolumab (240 mg every 2 weeks).
- No dose-limiting toxicities (DLTs) observed in part 1 (n=6).
- Treatment-related adverse events (TRAEs) occurred in all patients (n=30), most common being palmar-plantar erythrodysesthesia (60%).
- Objective response rate (ORR) was 66.7% (part 1) and 79.2% (part 2) by mRECIST.
- Median progression-free survival (PFS) was 9.07 months, and median overall survival (OS) was 26.94 months in part 2.
- Lenvatinib + nivolumab was well-tolerated and showed promising antitumor activity in advanced uHCC.
Non-invasive tests to guide hepatocellular carcinoma surveillance - PubMed
2 months ago
- Non-invasive tests like FIB-4 and liver stiffness measurement (LSM) are effective in predicting hepatocellular carcinoma (HCC) risk.
- FIB-4 scores ≥1.75 and >2.67 align with LSM thresholds of ≥10 kPa and ≥15 kPa, respectively, in identifying patients at risk for HCC.
- The study analyzed 6,143 patients and validated findings in the UK Biobank, showing FIB-4's comparable accuracy to LSM in predicting HCC.
- FIB-4 can serve as a practical tool for HCC surveillance, especially where LSM is unavailable.
- The findings support the use of FIB-4 in clinical practice to guide HCC surveillance strategies.
DysUFMylation reprograms immunosuppressive neutrophils to potentiate anti-PD-1 therapy in hepatocellular carcinoma - PubMed
2 months ago
- UFL1-mediated UFMylation is critical in remodeling the immune microenvironment of hepatocellular carcinoma (HCC).
- Low UFL1 expression enhances CD8+ T-cell infiltration and cytotoxicity while reducing tumor-associated neutrophil (TAN) infiltration and N2-like polarization.
- UFL1 deficiency impairs PRMT5 stability, inhibiting NF-κB p65 DNA binding and reducing CXCL8 expression, leading to decreased neutrophil infiltration and N2 polarization.
- Low UFL1 expression synergizes with anti-PD-1 therapy to prolong survival in HCC models.
- Pharmacologic inhibition of CXCL8-CXCR1/2 signaling with SX-682 mimics the effects of low UFL1 expression.
- Patients responding to immunotherapy show reduced UFL1, PRMT5, and CXCL8 expression, decreased neutrophil infiltration, elevated CD8+ T-cell activity, and lower serum CXCL8 levels.
- The UFL1-PRMT5-NF-κB p65-CXCL8 axis governs neutrophil-driven immunosuppression in HCC.
- CXCL8 is identified as a predictive biomarker and therapeutic target to optimize immunotherapy in HCC patients.
Glutamine Deprivation Triggers Tribbles Homolog 3 Dependent G-Quadruplex Resolution to Maintain DNA Repair and Tumor Survival - PubMed
2 months ago
- Glutamine is essential for tumor survival, but therapies targeting glutamine metabolism often fail due to adaptive resistance.
- TRIB3, a pseudokinase, is identified as a key mediator in hepatocellular carcinoma (HCC) cells' adaptation to glutamine deprivation.
- TRIB3 is upregulated under glutamine deprivation in a c-Jun-dependent manner, safeguarding DNA repair fidelity and preventing replication catastrophe.
- TRIB3 binds to G-quadruplex DNA (G4-DNA) structures, recruiting the helicase DDX5 to resolve them, maintaining DNA repair pathways.
- Depletion of TRIB3 or DDX5 leads to G4-DNA accumulation, increased DNA damage, and downregulation of DNA damage repair (DDR) pathways.
- TRIB3-DDX5 prevents G4-DNA accumulation at BRCA1 and RAD51AP1 promoter regions, ensuring transcription of homologous recombination (HR) pathway genes.
- In vivo, TRIB3 silencing suppresses HCC xenograft growth, increasing DNA damage and apoptosis under glutamine-deficient conditions.
- Clinically, TRIB3 overexpression in HCC correlates with poor prognosis, suggesting the TRIB3-DDX5-G4 axis as a therapeutic target.
Targeting tRNA-dependent tyrosine usage unveils a metabolic vulnerability in hepatocellular carcinoma - PubMed
2 months ago
- Hepatocellular carcinoma (HCC) maintains low tyrosine levels despite increased uptake and reduced metabolism.
- MYC-driven upregulation of YARS1 and tRNA-TyrGUA redirects tyrosine to translation in HCC.
- Restricting tyrosine translation availability (RTTA) mitigates tumorigenesis and extends survival.
- RTTA reduces tyrosine codon-dependent translation of NDUFB8 and SCD1, leading to complex I misassembly and ferroptosis.
- CRISPR screening identifies GPX4 and BCL2 loss enhances RTTA's ability to inhibit HCC.
- RTTA is a therapeutic strategy targeting tyrosine dependency in liver cancer.
Targeting FGFR1-regulated SPP1 signaling repolarizes immunosuppressive macrophages and sensitizes Hepatocellular Carcinoma to anti-PD-1 therapy - PubMed
2 months ago
- Targeting FGFR1-regulated SPP1 signaling repolarizes immunosuppressive macrophages and sensitizes Hepatocellular Carcinoma (HCC) to anti-PD-1 therapy.
- ICB resistance in HCC is associated with FGFR1 upregulation, activating MAPK signaling and inducing SPP1 expression, promoting M2-type macrophage polarization and suppressing T cell function.
- SPP1 knockdown or neutralization reduces macrophage accumulation and restores T cell infiltration in tumors.
- Pharmacological inhibition of FGFR1 with BGJ398 synergizes with anti-PD-1 therapy, enhancing antitumor efficacy in preclinical models.
- High FGFR1 expression correlates with poor responses to ICB in HCC patients, suggesting FGFR1 as a predictive biomarker.
BCLC classification and AI-based image quantification: What is meant to be will come together - but how and when?: BCLC and AI-based image quantification - PubMed
2 months ago
- The Barcelona Clinic Liver Cancer (BCLC) classification is a key tool for HCC prognosis and treatment selection.
- AI-based image quantification can enhance BCLC by extracting detailed imaging data automatically.
- Despite AI advancements in tumor volumetry and radiomics, clinical implementation faces technical and administrative challenges.
- Synergy between AI-quantified imaging and BCLC could improve HCC management but requires standardized validation and workflow integration.
HBx Promotes Liver Cancer Cells to Escape NK-92 Cell Attack by Mediating ADAM10 to Enzyme Cut MICA/B Shedding From Cancer Cell Membrane - PubMed
2 months ago
- HBx promotes MICA/B shedding from liver cancer cell membranes, aiding escape from NK-92 cell attacks.
- HBx upregulates ADAM10 activity, which cuts MICA/B from HCC cell surfaces, reducing immune detection.
- High expression of HBx, MICA/B, and HIF-1α observed in HBV-infected HCC tissues.
- Inhibitors LW-6 (HIF-1α) and GI254023X (ADAM10) reverse HBx effects, restoring MICA/B membrane levels.
- HBx overexpression increases HCC resistance to NK-92 cells and reduces cytokine secretion (IFN-γ, IL-2, IL-10).
- HBx activates HIF-1α pathway to regulate ADAM10, facilitating immune evasion in HCC.
Impaired glycosylation promotes rapid transition to hepatocellular carcinoma in model of diet induced steatotic liver disease - PubMed
2 months ago
- Obesity-linked steatosis is a significant risk factor for hepatocellular carcinoma (HCC).
- Hepatocyte-specific NgBR deletion in mice (N-LKO) leads to increased triacylglycerol (TAG) accumulation, inflammation, ER/oxidative stress, fibrosis, and HCC development with 100% penetrance after four months on a high-fat diet.
- Liver-specific knockout of DHDDS (D-LKO) and a knock-in model with a human NgBR mutation impairing cis-PTase activity also developed HCC under high-fat diet conditions, but with lower penetrance.
- NgBR deficiency promotes excessive hepatic TAG accumulation by enhancing lipid uptake and impairing VLDL secretion.
- Pharmacological inhibition of DGAT2, a key enzyme in TAG synthesis, prevents diet-induced liver damage and HCC burden in N-LKO mice.
- cis-PTase is identified as a critical suppressor of MASLD-HCC conversion, and DGAT2 inhibition is suggested as a potential therapeutic approach to delay HCC formation in advanced MASH.
β-catenin mutation reprograms ketone body metabolism to drive hepatocellular carcinoma metastasis and resistance to ketogenic therapy via transcriptional activation of OXCT1 - PubMed
2 months ago
- β-catenin mutation (S33Y) in hepatocellular carcinoma (HCC) leads to resistance to ketogenic therapy and promotes metastasis.
- OXCT1, a key enzyme in ketone body catabolism, is aberrantly activated by mutated β-catenin, driving ketolysis and metabolic reprogramming.
- Blocking OXCT1 in β-catenin-mutated HCC reverses ketogenic therapy resistance and reduces metastasis by lowering tumor glutamate levels.
- OXCT1 activation enhances HCC metastasis via p-STAT3 and epithelial-mesenchymal transition pathways.
- Targeting OXCT1 presents a potential therapeutic strategy for β-catenin-mutated HCC.
Synergistic immunotherapeutic effects of irreversible electroporation and CAR-NK cell therapy against hepatocellular carcinoma - PubMed
2 months ago
- CAR-NK cell therapy is a promising immunotherapeutic approach with strong cytotoxicity and safety.
- Hepatocellular carcinoma (HCC) has a suppressive tumor microenvironment (TME) that limits CAR-NK cell efficacy.
- Irreversible electroporation (IRE) reshapes the TME by inducing immunogenic cell death and releasing chemokines like CX3CL1.
- IRE-treated HCC cells show increased susceptibility to NK-mediated cytotoxicity due to elevated reactive oxygen species.
- Combining IRE with GPC3-targeted CAR-NK cells enhances tumor lysis in vitro and tumor regression in HCC models without systemic toxicity.
- The study proposes a clinically actionable treatment paradigm for overcoming resistance in solid tumors like HCC.
NPLOC4 Inhibition Remodels Tumor Microenvironment via M2-to-M1 Macrophage Reprogramming and Boosts Anti-PD-1 Response in Liver Cancer - PubMed
2 months ago
- NPLOC4 inhibition remodels the tumor microenvironment by reprogramming M2 macrophages to M1, enhancing anti-PD-1 response in liver cancer.
- NPLOC4+ TAMs inhibit antitumor immune responses by promoting RIG-I degradation, negatively impacting HCC patient prognosis.
- NPLOC4 suppresses the type I interferon pathway in TAMs, promotes M2 polarization, and reduces CD8+ T-cell infiltration, creating an immunosuppressive HCC microenvironment.
- Disulfiram/copper (DSF/Cu) targets NPLOC4, and combining DSF/Cu with PD-1 therapy significantly inhibits HCC growth.
- Targeting NPLOC4+ TAMs enhances resistance to anti-PD-1 therapy, presenting a novel immune target for HCC treatment.
USP1 promotes hepatocellular carcinoma progression by modulating mitophagy via stabilizing MCM3 to regulate the Keap1-Nrf2 axis - PubMed
2 months ago
- USP1 promotes hepatocellular carcinoma (HCC) progression by stabilizing MCM3 through deubiquitination.
- MCM3 upregulation in HCC suppresses tumor cell apoptosis and enhances mitophagy, aiding cancer progression.
- MCM3 binds to Keap1, disrupting the Keap1-Nrf2 interaction, which activates the Nrf2 signaling pathway to modulate mitophagy.
- Knockdown of MCM3 inhibits tumor growth in vivo, suggesting its role as a key oncoprotein in HCC.
- Targeting MCM3 could be a potential therapeutic strategy for liver cancer due to its influence on mitophagy and tumor progression.
A Unique Intercellular Feedforward Loop From HK1 to TGF-β1 Promotes the Progression of Hepatocellular Carcinoma - PubMed
2 months ago
- Hepatocellular carcinoma (HCC) progression is influenced by a unique intercellular feedforward loop involving HK1 and TGF-β1.
- Hepatic stellate cells (HSCs) secrete hexokinase 1 (HK1) via large extracellular vesicles (lEVs), which are taken up by HCC cells to boost glucose metabolism.
- Enhanced glucose metabolism in HCC cells reciprocally activates HSCs, creating a pro-tumourigenic fibrotic microenvironment.
- HK1 accelerates the hexosamine biosynthesis pathway, promoting N-glycosylation and secretion of TGF-β1 from HCC cells, which further activates HSCs.
- Disrupting this feedforward loop significantly inhibits HCC progression, suggesting a potential therapeutic strategy.
Metabolic reprogramming in cancer: dysregulation of glucose, lipid, and amino acid pathways and therapeutic opportunities - PubMed
2 months ago
- Metabolic reprogramming is a hallmark of cancer, including hepatocellular carcinoma (HCC).
- Cancer cells exhibit enhanced glucose and glutamine uptake, increased glycolysis, pentose phosphate pathway activity, de novo lipogenesis, and altered amino acid metabolism.
- Key signaling regulators involved in cancer metabolic reprogramming include mTORC1, c-Myc, HIF-1α, ATF4, NRF2, and SREBP1.
- The review highlights interconnections among metabolic pathways and signaling hubs that orchestrate metabolic crosstalk.
- Metabolic targets and metabolism-directed therapeutic agents with developmental potential are summarized, including TVB-2640 and CB-839 in clinical trials.
- Challenges include adverse effects on normal tissues and drug resistance driven by metabolic plasticity.
- Innovative strategies include combination therapy, overcoming resistance, early cancer detection, immunometabolism, and metabolomics.
Integrated multi-omics analysis reveals that MARCKS reprograms the immunosuppressive microenvironment to drive hepatocellular carcinoma progression - PubMed
2 months ago
- MARCKS is significantly upregulated in hepatocellular carcinoma (HCC) tissues and linked to aggressive features and poor prognosis.
- Integrated multi-omics analysis (bulk transcriptomics, single-cell RNA sequencing, spatial transcriptomics) reveals MARCKS's role in HCC.
- MARCKS expression is enriched in myeloid cells within the tumor microenvironment, promoting immunosuppression.
- MARCKS enhances JAK/STAT3 signaling and M2-like macrophage polarization, contributing to immune evasion.
- Silencing MARCKS reduces STAT3 phosphorylation, suppresses tumor growth, and decreases M2 macrophage polarization.
- MARCKS is identified as a potential therapeutic target for overcoming immunosuppression in HCC.

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#hepatocellular carcinoma

Plasma GPC3 reflects tumor GPC3 expression and predicts clinical outcomes in advanced HCC treated with atezolizumab + bevacizumab - PubMed

Multi-omics profiling reveals cholic acid-mediated immunosuppression driven by peritumoral ductular reactions in hepatocellular carcinoma - PubMed

Transcriptional factor ZMYM3 promotes hepatocellular carcinoma metastasis by upregulating CTTN and inducing invadopodia formation - PubMed

Asynchronous Transitions from High-Risk Hepatoblastoma to Carcinoma - PubMed

A Phase 1b Study of Lenvatinib plus Nivolumab in Patients with Unresectable Hepatocellular Carcinoma - PubMed

Non-invasive tests to guide hepatocellular carcinoma surveillance - PubMed

DysUFMylation reprograms immunosuppressive neutrophils to potentiate anti-PD-1 therapy in hepatocellular carcinoma - PubMed

Glutamine Deprivation Triggers Tribbles Homolog 3 Dependent G-Quadruplex Resolution to Maintain DNA Repair and Tumor Survival - PubMed

Targeting tRNA-dependent tyrosine usage unveils a metabolic vulnerability in hepatocellular carcinoma - PubMed

Targeting FGFR1-regulated SPP1 signaling repolarizes immunosuppressive macrophages and sensitizes Hepatocellular Carcinoma to anti-PD-1 therapy - PubMed

BCLC classification and AI-based image quantification: What is meant to be will come together - but how and when?: BCLC and AI-based image quantification - PubMed

HBx Promotes Liver Cancer Cells to Escape NK-92 Cell Attack by Mediating ADAM10 to Enzyme Cut MICA/B Shedding From Cancer Cell Membrane - PubMed

Impaired glycosylation promotes rapid transition to hepatocellular carcinoma in model of diet induced steatotic liver disease - PubMed

β-catenin mutation reprograms ketone body metabolism to drive hepatocellular carcinoma metastasis and resistance to ketogenic therapy via transcriptional activation of OXCT1 - PubMed

Synergistic immunotherapeutic effects of irreversible electroporation and CAR-NK cell therapy against hepatocellular carcinoma - PubMed

NPLOC4 Inhibition Remodels Tumor Microenvironment via M2-to-M1 Macrophage Reprogramming and Boosts Anti-PD-1 Response in Liver Cancer - PubMed

USP1 promotes hepatocellular carcinoma progression by modulating mitophagy via stabilizing MCM3 to regulate the Keap1-Nrf2 axis - PubMed

A Unique Intercellular Feedforward Loop From HK1 to TGF-β1 Promotes the Progression of Hepatocellular Carcinoma - PubMed

Metabolic reprogramming in cancer: dysregulation of glucose, lipid, and amino acid pathways and therapeutic opportunities - PubMed

Integrated multi-omics analysis reveals that MARCKS reprograms the immunosuppressive microenvironment to drive hepatocellular carcinoma progression - PubMed