Vascular Endothelial Growth Factor-D (VEGF-D): An Angiogenesis Bypass in Malignant Tumors

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(17), P. 13317 - 13317

Published: Aug. 28, 2023

Vascular endothelial growth factors (VEGFs) are the key regulators of vasculogenesis in normal and oncological development. VEGF-A is most studied angiogenic factor secreted by malignant tumor cells under hypoxic inflammatory stress, which made a rational target for anticancer therapy. However, inhibition monoclonal antibody drugs led to upregulation VEGF-D. VEGF-D was primarily described as lymphangiogenic factor; however, VEGF-D's blood potential comparable has already been demonstrated glioblastoma colorectal carcinoma. These findings suggested role facilitating bypassing anti-VEGF-A antiangiogenic Owing its high mitogenic ability, higher affinity VEGFR-2, expression cancer, might even be stronger driver and, hence, better therapeutic than VEGF-A. In this review, we summarized targetability an therapy cancer.

Language: Английский

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Recent Progress in Systemic Therapy for Advanced Hepatocellular Carcinoma

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 1259 - 1259

Published: Jan. 19, 2024

Patients with advanced hepatocellular carcinoma (HCC) have several systemic treatment options. There are many known risk factors for HCC, and although some, such as hepatitis C, now treatable, others not. For example, metabolic dysfunction-related chronic liver disease is increasing in incidence has no specific treatment. Underlying disease, drug resistance, an number of options without biomarkers all challenges selecting the best each patient. Conventional chemotherapy almost never used advanced-stage which instead treated immunotherapy, tyrosine kinase inhibitors, VEGF inhibitors. Immune checkpoint inhibitors targeting various receptors been or currently undergoing clinical evaluation. Ongoing trials three-drug regimens may be future HCC Other immune-modulatory approaches chimeric antigen receptor-modified T cells, bispecific antibodies, cytokine-induced killer natural vaccines early-stage trials. Targeted therapies remain limited but represent area potential growth. As we shift away from first-line sorafenib trial control arms should comprise a standard other than sorafenib, one that better comparator advancing therapies.

Language: Английский

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Integrating Single-Cell and Spatial Transcriptomics to Uncover and Elucidate GP73-Mediated Pro-Angiogenic Regulatory Networks in Hepatocellular Carcinoma

Research, Journal Year: 2024, Volume and Issue: 7

Published: Jan. 1, 2024

Hepatocellular carcinoma (HCC) was characterized as being hypervascular. In the present study, we generated a single-cell spatial transcriptomic landscape of vasculogenic etiology HCC and illustrated overexpressed Golgi phosphoprotein 73 (GP73) cells exerting cellular communication with vascular endothelial high pro-angiogenesis potential via multiple receptor-ligand interactions in process tumor development. Specifically, uncovered an interactive GP73-mediated regulatory network coordinated c-Myc, lactate, Janus kinase 2/signal transducer activator transcription 3 (JAK2/STAT3) pathway, endoplasmic reticulum stress (ERS) signals elucidated its pro-angiogenic roles vitro vivo. Mechanistically, found that GP73, pivotal hub gene, activated by histone lactylation which stimulated phosphorylation downstream STAT3 directly binding simultaneously enhancing glucose-regulated protein 78 (GRP78)-induced ERS. potentiates functions. Clinically, serum GP73 levels were positively correlated response to anti-angiogenic regimens essential for prognostic nomogram showing good predictive performance determining 6-month 1-year survival patients treated therapy. Taken together, aforementioned data mechanisms proved is crucial angiogenesis niche gene favorable treatment HCC.

Language: Английский

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Predicting Outcomes of Atezolizumab and Bevacizumab Treatment in Patients with Hepatocellular Carcinoma

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

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Serum FGF21 as predictor of response to atezolizumab and bevacizumab in HCC

JHEP Reports, Journal Year: 2025, Volume and Issue: 7(5), P. 101364 - 101364

Published: Feb. 20, 2025

Fibroblast growth factor 21 (FGF21) is a crucial regulator of cell metabolism. Tumour-secreted FGF21 has shown immune-checkpoint functions, and high levels are associated with poor prognosis for patients. However, its prognostic value impact on treatment response in patients hepatocellular carcinoma (HCC) treated inhibitors (ICIs) remain unclear. Thus, this study investigated the potential as marker whether traditional ICI-based therapy can improve levels. In retrospective multicentre study, unresectable HCC who received atezolizumab/bevacizumab NORTE group (n = 117) were classified into (≥915 pg/ml; n 29) non-high 88) groups. For validation, we an independent cohort 285). Overall survival, progression-free compared between without baseline The median overall survival (p <0.001) 0.045) significantly shorter than group. Independent analysis validated these results. cohort, (5.75 vs. 8.84 months; p 0.027) (14.13 22.08 durable (≥6 months) + complete rate was decreased 0.045). No patient level achieved response, whereas 4.1% (13/319) Multivariate Cox regression identified serum (hazard ratio 2.20, <0.001). Serum may be robust, non-invasive atezolizumab/bevacizumab. been reported to act secreted factor, elevated HCC. It not fully understood ICIs overcome shortened exhibited survival. These findings suggest robust indicator therapy. could implementation personalised strategies identifying optimal therapeutic options remains urgent critical clinical issue.

Language: Английский

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Myeloid cell path to malignancy: insights into liver cancer

Trends in cancer, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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Circulating miR-485-3p as a biomarker for VEGF-associated therapeutic response to atezolizumab plus bevacizumab in hepatocellular carcinoma

Journal of Gastroenterology, Journal Year: 2025, Volume and Issue: unknown

Published: April 3, 2025

Language: Английский

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Potential Correlation between Changes in Serum FGF21 Levels and Lenvatinib-Induced Appetite Loss in Patients with Unresectable Hepatocellular Carcinoma

Cancers, Journal Year: 2023, Volume and Issue: 15(12), P. 3257 - 3257

Published: June 20, 2023

Lenvatinib, used for unresectable hepatocellular carcinoma (HCC), causes appetite loss, but the underlying mechanisms, clinical impact, and predictive factors have been unclear. The endocrine factor FGF21 modulates is involved in cachexia. We evaluated association between level changes during lenvatinib treatment HCC loss. Sixty-three eligible patients who started 2018 2021 were included. analyzed levels at baseline; 1, 2, 4 weeks after initiation, before onset of Grade ≥ 2 lenvatinib-induced loss led to liver functional reserve deterioration disease progression a poor prognosis. Baseline characteristics serum similar with without However, change rate increased significantly post-lenvatinib initiation grade as compared those Similar significant increases observed prior onset. This suggests that can be predict greater risk marked provides insights into mechanisms HCC.

Language: Английский

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Advances in hepatocellular carcinoma drug resistance models

Frontiers in Medicine, Journal Year: 2024, Volume and Issue: 11

Published: July 31, 2024

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Surgery has been major treatment method for HCC owing to HCC’s poor sensitivity radiotherapy and chemotherapy. However, its effectiveness limited by postoperative tumour recurrence metastasis. Systemic therapy applied eliminate residual cells improve survival of patients with advanced HCC. Recently, emergence various novel targeted immunotherapeutic drugs significantly improved prognosis immunological therapies may not always produce complete long-lasting anti-tumour responses because heterogeneity drug resistance. Traditional patient-derived cell lines or animal models are used investigate resistance mechanisms identify that could reverse This study comprehensively reviewed established methods applications in-vivo in-vitro further understand in provide a model basis possible individualised therapy.

Language: Английский

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Association of proteinuria with improved prognosis in unresectable hepatocellular carcinoma treated with atezolizumab and bevacizumab, and the predictive role of serum vascular endothelial growth factor D levels: A multicenter retrospective study

Hepatology Research, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 25, 2024

Abstract Aim Atezolizumab/bevacizumab is a first‐line therapy for unresectable hepatocellular carcinoma (HCC). Among several adverse events, grade ≥2 proteinuria considered significant event that may cause bevacizumab interruption. Studies have shown might predict improved prognosis, although data are scarce and the association remains controversial, mechanisms predictive factors remain unclear. We aimed to clarify these. Methods In this multicenter retrospective study, we screened patients with HCC treated atezolizumab/bevacizumab. The prognostic impact of was examined in proper clinical preserved serum growth factor analysis. For biomarker analysis predicting proteinuria, baseline vascular endothelial (VEGF)‐A, VEGF‐C, VEGF‐D levels were analyzed. Results This study included 75 patients, 32 (42.7%) experienced proteinuria. No differences observed between those or without except aspartate transaminase alanine levels. Time‐dependent Cox proportional hazards revealed significantly associated better prognosis (hazard ratio 0.221; 95% confidence interval 0.082–0.592; p = 0.003). analysis, low VEGF‐C multivariate demonstrated level 0.101; 0.029–0.357; < 0.001). Conclusions Grade atezolizumab/bevacizumab indicates can help its occurrence. These findings managing events advanced

Language: Английский

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