Strategies to enhance the response of liver cancer to pharmacological treatments DOI
José J.G. Marı́n, Rocı́o I.R. Macı́as, Maitane Asensio

и другие.

AJP Cell Physiology, Год журнала: 2024, Номер 327(1), С. C11 - C33

Опубликована: Май 6, 2024

In contrast to other types of cancers, there is no available efficient pharmacological treatment improve the outcomes patients suffering from major primary liver i.e., hepatocellular carcinoma and cholangiocarcinoma. This dismal situation partly due existence in these tumors many different synergistic mechanisms resistance, accounting for lack response patients, not only classical chemotherapy but also more modern agents based on inhibition tyrosine kinase receptors (TKIs) stimulation immune against tumor using checkpoint inhibitors (ICIs). review summarizes efforts develop strategies overcome this severe limitation, including searching novel drugs derived synthetic, semisynthetic, or natural products with vectorial properties therapeutic targets increase drug uptake reduce export cancer cells. Besides, immunotherapy a promising line research that already starting be implemented clinical practice. Although less successful than foreseen future strategy treating cancers considerable. Similarly, epigenetic highly promising. Many “epidrugs,” able act “writer,” “reader,” “eraser” players, are currently being evaluated preclinical studies. Finally, gene therapy broad field fight chemoresistance, impressive advances recently achieved manipulation. sum, although present still dismal, reason hope non-too-distant future.

Язык: Английский

Hepatocellular carcinoma: signaling pathways, targeted therapy, and immunotherapy DOI Creative Commons
Xiaoting Luo, Xin He, Xingmei Zhang

и другие.

MedComm, Год журнала: 2024, Номер 5(2)

Опубликована: Фев. 1, 2024

Abstract Hepatocellular carcinoma (HCC) is the most common primary liver cancer with a high mortality rate. It regarded as significant public health issue because of its complicated pathophysiology, metastasis, and recurrence rates. There are no obvious symptoms in early stage HCC, which often leads to delays diagnosis. Traditional treatment methods such surgical resection, radiotherapy, chemotherapy, interventional therapies have limited therapeutic effects for HCC patients or metastasis. With development molecular biology immunology, signaling pathways immune checkpoint were identified main mechanism progression. Targeting these molecules has become new direction HCC. At present, combination targeted drugs inhibitors first choice advanced patients. In this review, we mainly focus on cutting‐edge research corresponding therapy immunotherapy great significance comprehensively understand pathogenesis search potential targets, optimize strategies

Язык: Английский

Процитировано

32
The Malignant Transformation of Viral Hepatitis to Hepatocellular Carcinoma: Mechanisms and Interventions DOI Creative Commons
Huimin Yuan, Ruochen Xu, Senlin Li

и другие.

MedComm, Год журнала: 2025, Номер 6(3)

Опубликована: Март 1, 2025

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality globally, predominantly associated with chronic hepatitis B virus (HBV) and C (HCV) infections. These infections drive persistent liver inflammation, culminating in cellular dysregulation, fibrosis, cancer. Despite advancements targeted therapies, drug resistance the lack reliable biomarkers for patient stratification still terribly hinder treatment viral HCC. To this end, review delves into intricate mechanisms underlying malignant transformation to HCC, including integration, genomic instability, epigenetic modifications, oxidative stress, gut microbiota dysbiosis, immune escape, abnormal signaling pathways, highlighting their complex interactions synergies. Cutting-edge preclinical clinical HCC management, lifestyle immunotherapies, gene-based approaches, innovative treatments, are further investigated, particular priority given therapeutic potential future applications overcoming current limitations. By synthesizing recent scientific insights, aims deepen understanding pathogenesis context hepatitis, paving way novel targets personalized strategies, ultimately improving outcomes.

Язык: Английский

Процитировано

1
MASLD-Related HCC: A Comprehensive Review of the Trends, Pathophysiology, Tumor Microenvironment, Surveillance, and Treatment Options DOI Creative Commons

Yuming Shi,

Erfan Taherifard, A.I. Saeed

и другие.

Current Issues in Molecular Biology, Год журнала: 2024, Номер 46(6), С. 5965 - 5983

Опубликована: Июнь 13, 2024

Hepatocellular carcinoma (HCC) represents a significant burden on global healthcare systems due to its considerable incidence and mortality rates. Recent trends indicate an increase in the worldwide of metabolic dysfunction-associated steatotic liver disease (MASLD) shift etiology HCC, with MASLD replacing hepatitis B virus as primary contributor new cases HCC. MASLD-related HCC exhibits distinct characteristics compared viral including unique immune cell profiles resulting overall more immunosuppressive or exhausted tumor microenvironment. Furthermore, is frequently identified older age groups among individuals cardiometabolic comorbidities. Additionally, greater percentage occur noncirrhotic patients those etiologies, hindering early detection. However, current clinical practice guidelines lack specific recommendations for screening patients. The evolving landscape management offers spectrum therapeutic options, ranging from surgical interventions locoregional therapies systemic treatments, across various stages disease. Despite ongoing debates, evidence does not support differences optimal treatment modalities based etiology. In this study, we aimed provide comprehensive overview literature trends, characteristics, implications,

Язык: Английский

Процитировано

6
Pharmacologically inducing anoikis offers novel therapeutic opportunities in hepatocellular carcinoma DOI Open Access
Yumin Wang,

Joshua S Fleishman,

Jinhua Wang

и другие.

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 176, С. 116878 - 116878

Опубликована: Июнь 5, 2024

Tumor metastasis occurs in hepatocellular carcinoma (HCC), leading to tumor progression and therapeutic failure. Anoikis is a matrix detachment-induced apoptosis, also known as cell death, mechanistically prevents cells from escaping their native extracellular metastasize new organs. Deciphering the regulators mechanisms of anoikis cancer urgently needed treat HCC. Several natural synthetic products induce HCC vivo models. Here, we first briefly summarize current understanding molecular regulation relevant involved metastasis. Then discuss potential pharmacological induction treatment against Finally, key limitations this paradigm propose possible strategies overcome them. Cumulatively review suggests that can be used promising modality

Язык: Английский

Процитировано

5
Radioresistance in Hepatocellular Carcinoma: Biological Bases and Therapeutic Implications DOI Open Access
Jianhui Wu, Xiaofang Zhao,

Bowen Ren

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(5), С. 1839 - 1839

Опубликована: Фев. 21, 2025

Hepatocellular carcinoma (HCC) is a malignant tumor with high morbidity and mortality. Radiotherapy technology common treatment modality that can be used in all stages of HCC. However, some cases, radiotherapy fails clinical practice mainly because the patient’s resistance to radiotherapy, creating bottleneck for future breakthroughs. HCC radiosensitivity primarily related DNA double-strand break repair, cellular autophagy, cell cycle, metabolism, hypoxic environmental regulators. Therefore, comprehensive understanding its molecular mechanisms will immense importance reversing radioresistance. In this review, we provide overview mechanism action on HCC, basis radiation modalities, prospects.

Язык: Английский

Процитировано

0
Carfilzomib inhibits the progression of hepatocellular cancer by upregulating GADD45α expression DOI Open Access
Mingxun Chen, Chen Xu,

Yifang Shui

и другие.

Oncology Letters, Год журнала: 2025, Номер 29(4), С. 1 - 14

Опубликована: Март 4, 2025

Hepatocellular carcinoma (HCC) ranks among the most prevalent and lethal cancers affecting humans. Currently, there are limited effective treatments available for HCC. Carfilzomib, a proteasome inhibitor, is known to exert anti-HCC activities; however, its underlying mechanisms of action remain unclear. In present study, efficacy carfilzomib against HCC was evaluated were explored. Cell Counting Kit-8, 5-ethynyl-2-deoxyuridine staining colony formation assays employed analyze antiproliferative effect on MHCC-97H Huh7 cells. Additionally, flow cytometry used assess cell cycle Transwell evaluate migration invasion. Western blotting utilized examine protein expression levels associated with arrest. Furthermore, short hairpin RNA (shRNA) transfection investigate role DNA damage inducible α (GADD45α) carfilzomib-induced A xenograft tumor model using nude mice activity in vivo. The findings demonstrated that inhibited proliferation, invasion both addition, caused arrest by suppressing cyclin A2, E1 cyclin-dependent kinases 2 4. Carfilzomib also upregulated GADD45α, activated MAPK pathway GADD45α through shRNA abolished growth To conclude, research revealed inhibits progression cells upregulating expression, suggesting could be potential chemotherapeutic agent

Язык: Английский

Процитировано

0
Discovery of Potent and Selective c-Met Degraders for Hepatocellular Carcinoma Treatment DOI
Wenjian Min,

Huanaoyu Yang,

Dawei Wang

и другие.

Journal of Medicinal Chemistry, Год журнала: 2024, Номер unknown

Опубликована: Июль 4, 2024

Targeting c-Met is a clinical trend for the precise treatment of HCC, but potential issue acquired drug resistance cannot be ignored. Targeted protein degradation technology has demonstrated promising prospects in disease and overcoming due to its special mechanism action. In this study, we designed synthesized two series novel degraders conducted systematic biological evaluation optimal compound H11. H11 exhibited good activity anti-HCC activity. Importantly, also more potent inhibitory against Ba/F3-TPR-MET-D1228N Ba/F3-TPR-MET-Y1230H cell lines than did tepotinib. summary, displayed as degrader may overcome type Ib inhibitors, making it new therapeutic strategy HCC with MET alterations.

Язык: Английский

Процитировано

4
Primary hepatic carcinosarcoma: a case report with insights from retrospective analysis of clinical characteristics and prognostic factors DOI Creative Commons
Zonglei Zhao, Tao Wang,

Zhexuan Sun

и другие.

Frontiers in Medicine, Год журнала: 2025, Номер 11

Опубликована: Янв. 10, 2025

Primary hepatic carcinosarcoma (HCS) is an extremely rare malignant tumor with carcinomatous and sarcomatous elements. Few reported cases of HCS exist, especially sufficient records to describe imaging pathological features, making the diagnosis, treatment, prognosis a significant challenge for physicians. Here, we report case spontaneous rupture as initial symptom in 77-year-old elderly male who was admitted right upper abdominal pain 8 days. The computed tomography enhancement scan revealed one intrahepatic mixed density massive, enhanced shadow located mainly outside liver. We performed hepatectomy segment 4 through laparotomy. postoperative pathology results demonstrated HCS. patient recovered smoothly discharged after surgery. However, experienced recurrence died 5 months This underscores importance identifying high-risk populations personalized treatment strategies cases.

Язык: Английский

Процитировано

0
Diagnostic value of a lactylation-related gene signature in hepatocellular carcinoma DOI Open Access

Jiajia Zhang,

Chunmei Dong,

Lili Wu

и другие.

Translational Cancer Research, Год журнала: 2025, Номер 14(1), С. 296 - 312

Опубликована: Янв. 1, 2025

The occurrence rate of liver cancer is increasing in recent years. significance lactylation tumor cells should not be neglected. This study aimed to discover a gene signature related that can used for diagnostic applications. Data were downloaded from Cancer Genome Atlas (TCGA), GSE14520, GSE84402, and GSE62232 datasets. Differential analysis random forest performed hepatocellular carcinoma (HCC). Receiver operating characteristic (ROC) curve was evaluate efficiency, logistic regression established obtain the risk score equation. Besides, expression genes identified by TCGA database verified real-time quantitative polymerase chain reaction (RT-PCR). In order analyze prognostic performance, patients diagnosed with HCC stratified into either high or low categories based on median score. addition, immunotherapy drug sensitivity groups assessed. performance model validated Gene Expression Omnibus (GEO) dataset. had worse outcomes than those database. ROC curves showed characteristics lactylation-related good predictive capability. Furthermore, we developed nomogram patients, utilizing data resources TCGA. Finally, terms assessing potency group lower Tumor Immune Dysfunction Exclusion (TIDE) score, indicating response immunotherapy. Our identification associated presents promising avenue development targeted immunotherapeutic strategies.

Язык: Английский

Процитировано

0
Nanotechnology-driven EGCG: bridging antioxidant and therapeutic roles in metabolic and cancer pathways DOI
Zahra Esmaeili,

Parisa Shavali Gilani,

Masood Khosravani

и другие.

Nanomedicine, Год журнала: 2025, Номер unknown, С. 1 - 16

Опубликована: Фев. 9, 2025

Epigallocatechin-3-gallate (EGCG), the primary polyphenol in green tea, is renowned for its potent antioxidant properties. EGCG interacts with various cellular targets, inhibiting cancer cell proliferation through apoptosis and cycle arrest induction, while also modulating metabolic pathways. Studies have demonstrated potential addressing development, obesity, diabetes. Given rising prevalence of diseases cancers, increasingly recognized as a promising therapeutic agent. This review provides comprehensive overview latest findings on effects both free nano-encapsulated mechanisms involved management prevention hyperlipidemia, diabetes, gastrointestinal (GI) cancers. The highlights role key signaling pathways, enhancing bioavailability nano-formulations, applications clinical settings.

Язык: Английский

Процитировано

0