Hepatocellular carcinoma: Advances in systemic therapies

F1000Research, Journal Year: 2024, Volume and Issue: 13, P. 104 - 104

Published: May 7, 2024

Advanced hepatocellular carcinoma (HCC) is traditionally associated with limited treatment options and a poor prognosis. Sorafenib, multiple tyrosine kinase inhibitor, was introduced in 2007 as first-in-class systemic agent for advanced HCC. After sorafenib, range of targeted therapies immunotherapies have demonstrated survival benefits the past 5 years, revolutionizing landscape More recently, evidence novel combinations agents distinct mechanisms has emerged. In particular, combination trials on atezolizumab plus bevacizumab durvalumab tremelimumab shown encouraging efficacy. Hence, international societies revamped their guidelines to incorporate new recommendations these agents. Aside from HCC, indications therapy are expanding. For example, therapeutics locoregional (trans-arterial chemoembolization or stereotactic body radiation therapy) promising early results downstaging Recent also explored role neoadjuvant borderline-resectable HCC adjuvant reduce recurrence risk after curative resection. Despite clinical trials, real-world efficacy specific patient subgroups (such patients cirrhosis, high bleeding risk, renal impairment, cardiometabolic diseases) remains uncertain. The effect liver disease etiology warrants further research. With an increased understanding pathophysiological pathways accumulation data, personalized decisions will be possible, field continue evolve.

Language: Английский

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Current Trends in Surgical Management of Hepatocellular Carcinoma

Cancers, Journal Year: 2023, Volume and Issue: 15(22), P. 5378 - 5378

Published: Nov. 12, 2023

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. Surgical management, including hepatic resection, liver transplantation, and ablation, offers the greatest potential for curative approach. This review aims to discuss recent advancements in HCC surgery identify unresolved issues field. Treatment selection relies on BCLC staging system, with surgical therapies primarily recommended early-stage disease. Recent studies have shown that patients previously considered unresectable, such as those portal vein tumor thrombus uncomplicated hypertension, may benefit from resection. Minimally invasive improved visualization techniques are also explored, alongside new optimizing future remnant, ex vivo hemorrhage control. Liver transplantation criteria, particularly long-standing Milan critically examined. Alternative criteria proposed tested specific regions presented. In context organ shortage, bridging therapy plays critical role preventing progression maintaining eligible transplantation. Lastly, we explore emerging ablation modalities, comparing them current standard, radiofrequency ablation. conclusion, this comprehensive provides insights into trends prospects management HCC, highlighting areas require further investigation.

Language: Английский

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Upgraded theragnostic strategies of multivariate nano gold in the management of hepatocellular carcinoma

Nano-Structures & Nano-Objects, Journal Year: 2024, Volume and Issue: 40, P. 101342 - 101342

Published: Sept. 24, 2024

Language: Английский

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Multiple Subcutaneous Metastases in Endometrial Cancer Treated With Systemic Chemotherapy: A Case Report and Review of the Literature

Cureus, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 4, 2025

Subcutaneous metastasis of endometrial cancer (EC) is an exceedingly rare phenomenon, and the mechanisms underlying its pathogenesis remain insufficiently elucidated. We report case a 69-year-old multiparous woman diagnosed with stage IB EC, histologically classified as grade 3 endometrioid clear cell carcinoma. Approximately one month following primary surgical intervention, patient developed subcutaneous masses on her back, axilla, buttock. Histopathological evaluation, in conjunction PET-CT, confirmed systemic recurrence EC. She was subsequently treated combination paclitaxel carboplatin, remarkable therapeutic response; after six cycles chemotherapy, nearly all metastatic sites exhibited complete resolution. then transitioned to regimen lenvatinib pembrolizumab. However, week initiation this treatment, she hepatic encephalopathy, which presumed be lenvatinib-induced, successfully managed aminoleban injections, resulting full recovery consciousness. Follow-up diagnostic imaging response therapy. The currently receiving pembrolizumab maintenance therapy has remained recurrence-free for 18 months. While no standardized protocol exists management EC due extremely low incidence, provides evidence potential efficacy chemotherapy combined targeted immunotherapy treatment unresectable metastases

Language: Английский

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Effectiveness of regorafenib in second-line therapy for advanced hepatocellular carcinoma: A systematic review and meta-analysis

Medicine, Journal Year: 2025, Volume and Issue: 104(4), P. e41356 - e41356

Published: Jan. 24, 2025

Background: In patients with advanced hepatocellular carcinoma (HCC) following sorafenib failure, regorafenib has been used as an initial second-line drug. It is unclear the real efficacy and safety of sorafenib-regorafenib sequential therapy compared to placebo or other treatment (cabozantinib nivolumab placebo) in HCC. Methods: Four electronic databases (PubMed, Embase, Web Science, Ovid) were systematically searched for eligible articles from their inception July, 2024. Included selected based on strict eligibility criteria. Review Manager 5.4 software performed statistical analysis. Results: Ten studies 2349 HCC whom 1370 received treatment, 979 underwent cabozantinb, meta-analysis. The results our systematic review meta-analysis found could significantly prolong overall survival (standardized mean difference [SMD] = 0.16, 95% CI 0.02 0.29, P .02) than failure. No significant progression-free (SMD −0.03; −0.13 0.06; .53), response rate (risk ratio [RR] 0.59; 0.24 1.47; .26), disease control (RR 1.23; 0.7 2.16; .48) between 2 groups. Subgroup analysis demonstrated that better 0.38; 0.61; < .0001). Conclusions: Compared placebo), seemed be more effective who have not responded treatment.

Language: Английский

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PKM splice-switching ASOs induce upregulation of dual-specificity phosphatases and dephosphorylation of ERK1/2 in hepatocellular carcinoma

Journal of Biological Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108345 - 108345

Published: Feb. 1, 2025

Language: Английский

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Silibinin-Conjugated Galactose Dendrimers for Targeted Treatment of Hepatocellular Carcinoma

ACS Applied Materials & Interfaces, Journal Year: 2025, Volume and Issue: unknown

Published: March 27, 2025

Hepatocellular carcinoma (HCC) remains one of the most prevalent and lethal forms liver cancer, contributing significantly to global cancer-related mortality. Conventional treatments, including surgical resection, transplantation, systemic therapies such as multikinase inhibitors immune checkpoint inhibitors, often face limitations toxicity drug resistance, emphasizing urgent need for more effective therapeutic strategies. In this study, we developed a galactose-functionalized dendrimer (Gal24) conjugated with natural flavonoid, silibinin, (Gal24-Sil), HCC therapy. our previous Gal24 target hepatocytes in vivo. Here, further demonstrated that conjugation silibinin platform enhanced its solubility efficacy. vitro studies Gal24-Sil conjugates improved anticancer efficacy HepG2 Hep3B cancer cells. The conjugate induced an inflammatory response reactive oxygen species (ROS) generation, triggering cellular apoptosis necrosis. Furthermore, effectively reduced cell proliferation by promoting mitochondrial membrane potential (MMP) depolarization inducing DNA damage. Our findings demonstrate promising nanoplatform therapy, offering over free Silibinin. This study highlights broader applicability addressing various diseases.

Language: Английский

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Atezolizumab Plus Bevacizumab Versus Lenvatinib for Hepatocellular Carcinoma: A Systematic Review and Meta‐Analysis

The Journal of Clinical Pharmacology, Journal Year: 2024, Volume and Issue: 64(6), P. 643 - 651

Published: Feb. 4, 2024

Abstract Hepatocellular carcinoma (HCC) is often diagnosed in advanced stages. Following sorafenib, lenvatinib (LENV) has been approved as a first‐line treatment option for unresectable HCC. In the past few years, at least 9 large‐scale cohort studies have examined efficacy and safety of LENV compared to atezolizumab plus bevacizumab (ATE/BEV) HCC, but there currently no direct meta‐analysis conducted comprehensive consolidation. To provide most updated clinical ATE/BEV versus patients with Our comparing HCC were systematically searched PubMed, Embase, Web Science from inception February 2023. Outcomes measured overall survival (OS), progression‐free (PFS), mortality, complete response (CR), partial (PR), objective rate (ORR), disease control (DCR), progressive (PD), stable (SD), adverse events (AEs). Seven eligible involving 4428 (1569 group 2859 group) included narrative synthesis. All baseline characteristics similar between 2 groups except Child‐Pugh class B. Ultimately, our showed that had longer OS PFS than group. Moreover, on more likely achieve SD, whereas those PR.

Language: Английский

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Changing treatment landscape associated with improved survival in advanced hepatocellular carcinoma: a nationwide, population-based study

European Journal of Cancer, Journal Year: 2023, Volume and Issue: 192, P. 113248 - 113248

Published: July 21, 2023

Language: Английский

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REVIEWING ADVANCES IN UNDERSTANDING AND TARGETING THE MAPK SIGNALING PATHWAY IN HEPATOCELLULAR CARCINOMA PROGRESSION AND THERAPEUTICS

Agrobiological Records, Journal Year: 2024, Volume and Issue: 15, P. 103 - 116

Published: Jan. 1, 2024

Hepatocellular carcinoma (HCC) is a severe and increasingly prevalent health issue affecting individuals globally. Recent research endeavors in the clinical domains have lately focused more on MAPK signaling pathway HCC. Activating mutations RAS RAF genes, which greatly activate malignancies, are rare HCC patients, yet over 50% of them activated pathway. This suggests that other factors may be responsible for activation important to carcinogenesis, it often altered human cancers. The drug resistance targeted therapy against RTKs arise from downstream components (RAS, RAF, MEK, ERK), resistant within RTKs, additional alternative pathways like PI3K YAP also develop resistance. Epigenetic processes chromatin remodeling crucial pharmacological tolerance regulation. review will focus latest developments our knowledge cellular molecular pathway, as well possible treatment approaches specifically target this relation study investigates efficacy molecular-targeted treatments, including tyrosine kinase inhibitors immunological checkpoint highlights use combination

Language: Английский

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