Traditional Chinese medicine and natural products in management of hepatocellular carcinoma: Biological mechanisms and therapeutic potential

Pharmacological Research, Journal Year: 2025, Volume and Issue: unknown, P. 107733 - 107733

Published: April 1, 2025

Hepatocellular carcinoma (HCC), originating from hepatocytes, is the most common type of primary liver cancer. HCC imposes a significant global health burden with high morbidity and mortality, making it critical public concern. Surgical interventions, including hepatectomy transplantation, are pivotal in achieving long-term survival for patients HCC. Additionally, ablation therapy, endovascular interventional radiotherapy, systemic anti-tumor therapies commonly employed. However, these treatment modalities often associated considerable challenges, postoperative recurrence rates adverse effects. Traditional Chinese medicine (TCM) natural products have been utilized centuries as complementary approach managing its complications, demonstrating favorable clinical outcomes. Various bioactive compounds derived TCM identified purified, their mechanisms action extensively investigated. This review aims to provide comprehensive up-to-date evaluation efficacy TCM, active constituents management Particular emphasis placed on elucidating potential molecular therapeutic targets agents, roles inhibiting cell proliferation, inducing apoptosis pyroptosis, suppressing tumor invasion metastasis, restraining angiogenesis within tissues.

Language: Английский

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Study protocol: Fecal Microbiota Transplant combined with Atezolizumab/Bevacizumab in Patients with Hepatocellular Carcinoma who failed to achieve or maintain objective response to Atezolizumab/Bevacizumab – the FAB-HCC pilot study

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(4), P. e0321189 - e0321189

Published: April 15, 2025

Background The gut microbiota is often altered in chronic liver diseases and hepatocellular carcinoma (HCC), increasing evidence suggests that it may influence response to cancer immunotherapy. Strategies modulate the microbiome (i.e., fecal transplant (FMT)) help improve efficacy of immune checkpoint inhibitors (ICIs) or even overcome resistance ICIs. Here, we describe design rationale FAB-HCC, a single-center, single-arm, phase II pilot study assess safety, feasibility, FMT from patients with HCC who responded PD-(L)1-based immunotherapy healthy donors failed achieve maintain atezolizumab plus bevacizumab. Methods In this (ClinicalTrials.gov identifier: NCT05750030), plan include 12 advanced atezolizumab/bevacizumab. Patients will receive single via colonoscopy individuals, followed by atezolizumab/bevacizumab every 3 weeks. primary endpoint measured incidence severity treatment-related adverse events. main secondary efficacy, as assessed best radiological according RECISTv1.1 mRECIST. Additional exploratory endpoints data on effect recipient microbiota, well metagenomic analysis stool samples, analyses circulating cells serum proteomic, metabolomic lipidomic signatures. Discussion results define potential add-on intervention systemic treatment HCC, resistance. Trial registration EudraCT Number: 2022-000234-42 Clinical trial registry & ID: ClinicalTrials.gov NCT05750030 (Registration date: 16.01.2023)

Language: Английский

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Advancements in Diagnostics and Therapeutics for Cancer of Unknown Primary in the Era of Precision Medicine

MedComm, Journal Year: 2025, Volume and Issue: 6(5)

Published: April 16, 2025

ABSTRACT Cancer of unknown primary (CUP), a set histologically confirmed metastases that cannot be identified or traced back to its despite comprehensive investigations, accounts for 2–5% all malignancies. CUP is the fourth leading cause cancer‐related deaths worldwide, with median overall survival (OS) 3–16 months. has long been challenging diagnose principally due occult properties site. In current era molecular diagnostics, advancements in methodologies based on cytology, histology, gene expression profiling (GEP), and genomic epigenomic analysis have greatly improved diagnostic accuracy CUP, surpassing 90%. Our center conducted world's first phase III trial demonstrated progression‐free favorable OS by GEP‐guided site‐specific treatment setting foundation first‐line management CUP. this review, we detailed epidemiology, etiology, pathogenesis, as well histologic, genetic, clinical characteristics We also provided an overview diagnostics therapeutics over past 50 years. Moving forward, propose optimizing modalities exploring further‐line regimens two focus areas future studies

Language: Английский

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Self-delivery photothermal-boosted-nanobike multi-overcoming immune escape by photothermal/chemical/immune synergistic therapy against HCC

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: March 29, 2024

Abstract Immune checkpoint inhibitors (ICIs) combined with antiangiogenic therapy have shown encouraging clinical benefits for the treatment of unresectable or metastatic hepatocellular carcinoma (HCC). Nevertheless, therapeutic efficacy and wide applicability remain a challenge due to “cold” tumors’ immunological characteristics. Tumor immunosuppressive microenvironment (TIME) continuously natural force immune escape by extracellular matrix (ECM) infiltration, tumor angiogenesis, cell proliferation. Herein, we proposed novel concept multi-overcoming maximize ICIs against HCC. A self-delivery photothermal-boosted-NanoBike (BPSP) composed black phosphorus (BP) tandem-augmented anti-PD-L1 mAb plus sorafenib (SF) is meticulously constructed as triple combination strategy. The simplicity BPSP's composition, no additional ingredients added, makes it easy prepare presents promising marketing opportunities. (1) NIR-II-activated BPSP performs photothermal (PTT) remodels ECM depleting collagen I, promoting deep penetration therapeutics cells. (2) PTT promotes SF release exerts anti-vascular effects down-regulates PD-L1 via RAS/RAF/ERK pathway inhibition, enhancing in overcoming evasion. (3) Anti-PD-L1 block PD1/PD-L1 recognition PTT-induced ICD initiates effector T cells increases response rates mAb. Highly-encapsulated converted 'cold' tumors into 'hot' ones, improved CTL/Treg ratio, cured orthotopic HCC mice. Thus, offers new possibilities advancing immunotherapies, photothermal/chemical/immune synergistic shows promise development Graphical

Language: Английский

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Programmed Death Ligand 1 Expression in Circulating Tumor Cells as a Predictor and Monitor of Response to Atezolizumab plus Bevacizumab Treatment in Patients with Hepatocellular Carcinoma

Cancers, Journal Year: 2024, Volume and Issue: 16(9), P. 1785 - 1785

Published: May 6, 2024

There remains no reliable biomarker of therapeutic efficacy in hepatocellular carcinoma (HCC) for the PD-L1 inhibitor atezolizumab and bevacizumab (Atezo/Bev). Circulating tumor cells (CTCs) enable serial collection living cells. Pre-treatment CTC gene expression changes histology were evaluated to identify predictors response Atezo/Bev. Peripheral blood from 22 patients with HCC treated Atezo/Bev 24 lenvatinib was serially collected. The RNA CTCs analyzed using qRT-PCR. Higher pre-treatment associated improved prognosis treatment, but not lenvatinib. correlation between that liver biopsy specimens scored imaging software. Furthermore, dynamically altered by Atezo/Bev, decreasing during effective increasing upon progression. CTC-derived collected indicates higher at baseline 3.9 times more responsive treatment. Therefore, levels are an accurate predictor may be a monitorable reflect

Language: Английский

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