Immune checkpoint inhibition (ICI) in current systemic therapies for hepatocellular carcinoma (HCC) DOI Creative Commons
Florian van Bömmel, Thomas Berg, Florian Lordick

et al.

ESMO Gastrointestinal Oncology, Journal Year: 2023, Volume and Issue: 1, P. 27 - 39

Published: Oct. 1, 2023

Immune checkpoint inhibition (ICI) has revolutionized cancer therapy, including treatment of hepatocellular carcinoma (HCC) which comprises 80%-90% all liver cancers, the third most common cause cancer-related death worldwide. The main targeted pathways are cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) and programmed cell protein 1 (PD-1)/programmed death-ligand (PD-L1) checkpoints. Blockade CTLA-4 with monoclonal antibodies leads to an activation increase in effector T cells that can interact tumor cells. Additionally, inhibitory regulatory reduced, leading immunosupportive microenvironment. PD-1/PD-L1 reduces immunosuppression directly within tissue reactivates immune response Recently, HIMALAYA trial shown dual ICI CTLA-4-blocking antibody tremelimumab PD-L1-directed durvalumab (STRIDE regimen) is superior sorafenib regarding efficacy safety advanced HCC unprecedented long-term survival data for these patients. combination (atezolizumab) anti-vascular endothelial growth factor (bevacizumab) significantly improved outcomes compared been clinical use since 2020. Looking at outcome measures ICI, radiologically assessed endpoints such as progression-free objective rate only modestly correlate overall survival. modified RECIST criteria seem better identify responders conventional imaging evaluation criteria. So far, predictive biomarkers a robust understanding impact underlying diseases largely lacking. An accurate stratification patients based on etiology potential further improve HCC.

Language: Английский

Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline Update DOI
John D. Gordan, Erin B. Kennedy, Ghassan K. Abou‐Alfa

et al.

Journal of Clinical Oncology, Journal Year: 2024, Volume and Issue: 42(15), P. 1830 - 1850

Published: March 19, 2024

To update an evidence-based guideline to assist in clinical decision-making for patients with advanced hepatocellular carcinoma (HCC).

Language: Английский

Citations

75
Phenotypes of Metabolic Dysfunction–Associated Steatotic Liver Disease–Associated Hepatocellular Carcinoma DOI
Jesús Rivera‐Esteban, Sergio Muñoz, Mónica Higuera

et al.

Clinical Gastroenterology and Hepatology, Journal Year: 2024, Volume and Issue: 22(9), P. 1774 - 1789.e8

Published: April 10, 2024

Language: Английский

Citations

10
The current status and future of targeted-immune combination for hepatocellular carcinoma DOI Creative Commons

Liyuan Hao,

Shenghao Li,

Fanghang Ye

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Aug. 5, 2024

Hepatocellular carcinoma (HCC) is one of the most common cancers and third leading cause death worldwide. surgery, transarterial chemoembolization (TACE), systemic therapy, local ablation radiotherapy, targeted drug therapy with agents such as sorafenib. However, tumor microenvironment liver cancer has a strong immunosuppressive effect. Therefore, new treatments for are still necessary. Immune checkpoint molecules, programmed death-1 (PD-1), death-ligand 1 (PD-L1), cytotoxic T lymphocyte antigen-4 (CTLA-4), along high levels cytokines, induce cell inhibition key mechanisms immune escape in HCC. Recently, immunotherapy based on inhibitors (ICIs) monotherapy or combination tyrosine kinase inhibitors, anti-angiogenesis drugs, chemotherapy agents, topical therapies offered great promise treatment cancer. In this review, we discuss latest advances ICIs combined drugs (targeted-immune combination) other targeted-immune regimens patients advanced HCC (aHCC) unresectable (uHCC), provide an outlook future prospects. The literature reviewed spans last five years includes studies identified using keywords "hepatocellular carcinoma," "immune inhibitors," "targeted therapy," "combination "immunotherapy".

Language: Английский

Citations

9
Role of hepatotropic viruses in promoting hepatocellular carcinoma—current knowledge and recent advances DOI

Piotr Starnawski,

Klaudia Nowak,

Zuzanna Augustyn

et al.

Medical Oncology, Journal Year: 2025, Volume and Issue: 42(4)

Published: March 17, 2025

Language: Английский

Citations

1
Current Landscape of Immune Checkpoint Inhibitor Therapy for Hepatocellular Carcinoma DOI Creative Commons
Samantha M. Ruff, Ashish Manne, Jordan M. Cloyd

et al.

Current Oncology, Journal Year: 2023, Volume and Issue: 30(6), P. 5863 - 5875

Published: June 18, 2023

The liver maintains a balance between immune tolerance and activation in its role as filtration system. Chronic inflammation disrupts this microenvironment, thereby allowing for the rise progression of cancer. Hepatocellular carcinoma (HCC) is tumor generally diagnosed setting chronic disease. When early, primary treatment surgical resection, transplantation, or directed therapies. Unfortunately, patients with HCC often present at an advanced stage poor function, limiting options. To further complicate matters, most systemic therapies are relatively limited ineffective among Recently, IMbrave150 trial demonstrated that combination atezolizumab bevacizumab was associated better survival compared to sorafenib HCC. As such, now recommended first-line therapy these patients. Tumor cells work create immunotolerant environment by preventing stimulatory immunoreceptors upregulating expression proteins bind inhibitory immunoreceptors. ICIs block interactions bolster anti-tumor function We herein provide overview use

Language: Английский

Citations

14
Predicting Outcomes of Atezolizumab and Bevacizumab Treatment in Patients with Hepatocellular Carcinoma DOI Open Access
Ji Won Han, Jeong Won Jang

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(14), P. 11799 - 11799

Published: July 22, 2023

A combination of atezolizumab with bevacizumab (AB) is the first regimen that has shown superiority compared to sorafenib and now being used as systemic treatment choice for hepatocellular carcinoma (HCC) patients Barcelona Liver Cancer Clinic stage C. However, a considerable number do not achieve survival or significant responses, indicating need identify predictive biomarkers initial on-treatment decisions in HCC receiving AB. In this manuscript, we summarized current data from both experimental clinical studies. This review will be beneficial clinicians researchers practice well those designing experimental, translational,

Language: Английский

Citations

12
The evolution of immune checkpoint inhibitor combinations in advanced hepatocellular carcinoma – A systematic review DOI
Brandon M. Meyers, Jennifer J. Knox, David Liu

et al.

Cancer Treatment Reviews, Journal Year: 2023, Volume and Issue: 118, P. 102584 - 102584

Published: May 27, 2023

Language: Английский

Citations

11
Neoadjuvant therapies in resectable hepatocellular carcinoma: Exploring strategies to improve prognosis DOI Open Access
Yanan Ma, Xuemei Jiang, Peipei Song

et al.

BioScience Trends, Journal Year: 2024, Volume and Issue: 18(1), P. 21 - 41

Published: Feb. 19, 2024

Hepatocellular carcinoma (HCC), a challenging malignancy, often necessitates surgical intervention, notably liver resection. However, the high recurrence rate, reaching 70% within 5 years post-resection, significantly impacts patient outcomes. Neoadjuvant therapies aim to preoperatively address this challenge, reducing lesion size, improving resection rates, deactivating potential micro-metastases, and ultimately lowering postoperative rates. This review concentrates on advances in research clinical use of neoadjuvant for HCC, with particular attention immune checkpoint inhibitors (ICIs) targeting programmed cell death-1 (PD-1), death ligand-1 (PD-L1), cytotoxic T-lymphocyte-associated protein-4 (CTLA-4). Ongoing studies exploring immunotherapy combined tyrosine kinase inhibitor (TKI), interventional therapy, radiotherapy, other modalities offer promising insights into overcoming resistance monotherapies. In summary, hold significant promise terms prognosis patients HCC enhancing long-term survival, particularly through innovative combination strategies.

Language: Английский

Citations

4
Overcoming Resistance to Immune Checkpoint Blockade in Liver Cancer with Combination Therapy: Stronger Together? DOI Creative Commons

Wiebke Werner,

Maria Kuzminskaya,

Isabella Lurje

et al.

Seminars in Liver Disease, Journal Year: 2024, Volume and Issue: 44(02), P. 159 - 179

Published: May 1, 2024

Primary liver cancer, represented mainly by hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (CCA), is one of the most common deadliest tumors worldwide. While surgical resection or transplantation are best option in early disease stages, these often present advanced stages systemic treatment required to improve survival time. The emergence immune checkpoint inhibitor (ICI) therapy has had a positive impact especially on cancers, thereby establishing immunotherapy as part first-line HCC CCA. Nevertheless, low response rates reflect usually cold immunosuppressed tumor microenvironment primary cancer. In this review, we aim summarize mechanisms resistance leading escape with special focus composition both CCA, also reflecting recent important developments ICI combination therapy. Furthermore, discuss how ICIs established cancer treatments (e.g. multikinase inhibitors chemotherapy) well more complex combinations state-of-the-art therapeutic concepts may reshape microenvironment, higher long-lasting antitumor immunity for patients.

Language: Английский

Citations

4
Risk of Bleeding in Hepatocellular Carcinoma Patients Treated with Atezolizumab/Bevacizumab: A Systematic Review and Meta-Analysis DOI Creative Commons

Young‐Gi Song,

Kyeong-Min Yeom,

Eun Ae Jung

et al.

Liver Cancer, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 11

Published: May 22, 2024

<b><i>Introduction:</i></b> The combination of atezolizumab/bevacizumab has emerged as an effective first-line treatment for advanced hepatocellular carcinoma (HCC). However, this therapy is potentially associated with bleeding complications, warranting a comprehensive analysis their incidence and severity. This meta-analysis aims to synthesize available evidence from clinical trials observational studies quantify the prevalence following administration. <b><i>Methods:</i></b> focused on HCC using atezolizumab/bevacizumab, particularly examining complications. It determined post-administration compared risk ratio tyrosine kinase inhibitors (sorafenib or lenvatinib). Risk factors complications were also evaluated. <b><i>Results:</i></b> From 28 involving 3,895 patients, pooled side effects was 8.42% (95% CI: 5.72–11.54). Grade III IV occurred in 4.42% 2.64–6.10) grade V observed 2.06% 0.56–4.22). Gastrointestinal bleeding, predominantly variceal, most common, 5.48% 3.98–7.17). Subgroup indicated variability rates based study design geographical location. Atezolizumab/bevacizumab exhibited 2.11 times higher 1.21–3.66). Meta-regression identified high body mass index (BMI) proportion albumin-bilirubin (ALBI) 3 significant <b><i>Conclusion:</i></b> carries heightened gastrointestinal exceeding that inhibitors. High BMI ALBI are key predictors emphasizing need cautious patient selection monitoring.

Language: Английский

Citations

4