Hepatocellular Carcinoma: Old and Emerging Therapeutic Targets

Cancers, Год журнала: 2024, Номер 16(5), С. 901 - 901

Опубликована: Фев. 23, 2024

Liver cancer, predominantly hepatocellular carcinoma (HCC), globally ranks sixth in incidence and third cancer-related deaths. HCC risk factors include non-viral hepatitis, alcohol abuse, environmental exposures, genetic factors. No specific alterations are unequivocally linked to tumorigenesis. Current standard therapies surgical options, systemic chemotherapy, kinase inhibitors, like sorafenib regorafenib. Immunotherapy, targeting immune checkpoints, represents a promising avenue. FDA-approved checkpoint such as atezolizumab pembrolizumab, show efficacy, combination enhance clinical responses. Despite this, the treatment of (HCC) remains challenge, complex tumor ecosystem immunosuppressive microenvironment associated with it hamper efficacy available therapeutic approaches. This review explores current advanced approaches treat HCC, considering both known new potential targets, especially derived from proteomic analysis, which is today considered most approach. Exploring novel strategies, this discusses antibody drug conjugates (ADCs), chimeric antigen receptor T-cell therapy (CAR-T), engineered antibodies. It then reports systematic analysis main ligand/receptor pairs molecular pathways reported be overexpressed cells, highlighting their limitations. Finally, TGFβ, one targets microenvironment.

Язык: Английский

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Single-cell transcriptomic analysis reveals efferocytosis signature predicting immunotherapy response in hepatocellular carcinoma

Digestive and Liver Disease, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

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Interleukin-6 in Hepatocellular Carcinoma: A Dualistic Point of View

Biomedicines, Год журнала: 2023, Номер 11(10), С. 2623 - 2623

Опубликована: Сен. 24, 2023

Hepatocellular Carcinoma (HCC) is a pressing health concern, demanding deep understanding of various mediators’ roles in its development for therapeutic progress. Notably, interleukin-6 (IL-6) has taken center stage investigations due to intricate and context-dependent functions. This review delves into the dual nature IL-6 HCC, exploring seemingly contradictory as both promoter an inhibitor disease progression. We dissect pro-tumorigenic effects IL-6, including impact on tumor growth, angiogenesis, metastasis. Concurrently, we examine anti-tumorigenic attributes, such role immune response activation, cellular senescence induction, surveillance. Through comprehensive exploration interactions between microenvironment, this highlights need nuanced comprehension signaling HCC. It underscores importance tailored strategies that consider dynamic stages diverse surroundings within microenvironment. Future research directions aimed at unraveling multifaceted mechanisms HCC hold promise developing more effective treatment improving patient outcomes.

Язык: Английский

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Current Perspectives on the Molecular and Clinical Relationships between Primary Biliary Cholangitis and Hepatocellular Carcinoma

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(4), С. 2194 - 2194

Опубликована: Фев. 12, 2024

Primary biliary cholangitis (PBC) is an autoimmune liver disease characterised by the immune-mediated destruction of small and medium intrahepatic bile ducts, with variable outcomes progression. This review summarises state art regarding risk neoplastic progression in PBC patients, a particular focus on molecular alterations present hepatocellular carcinoma (HCC), which most frequent cancer these patients. Major factors are male gender, viral infections, e.g., HBV HCV, non-response to UDCA, high alcohol intake, as well some metabolic-associated factors. Overall, HCC development significantly more patients advanced histological stages, being related cirrhosis. It seems be fundamental importance unravel eventual dysfunctional pathways that may used biomarkers for development. In near future, this will possibly take advantage artificial intelligence-designed algorithms.

Язык: Английский

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Re-exploration of immunotherapy targeting EMT of hepatocellular carcinoma: Starting from the NF-κB pathway

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 174, С. 116566 - 116566

Опубликована: Апрель 16, 2024

Hepatocellular carcinoma (HCC) is the fifth most common malignancies worldwide, and its high morbidity mortality have brought a heavy burden to global public health system. Due concealment of onset, limitation treatment, acquisition multi-drug resistance radiation resistance, treatment HCC cannot achieve satisfactory results. Epithelial mesenchymal transformation (EMT) key process that induces progression, distant metastasis, therapeutic variety malignant tumors, including HCC. Therefore, targeting EMT has become promising tumor immunotherapy method for The NF-κB pathway regulatory EMT. Targeting this shown potential inhibit infiltration, invasion, resistance. At present, there are still some controversies about new ideas combined therapy, which need be further explored. This article reviews progress in improving development cells by exploring mechanism regulating

Язык: Английский

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Perfluorooctane sulfonate-induced Sertoli cell injury through c-Jun N-terminal kinase: a study by RNA-Seq

AJP Cell Physiology, Год журнала: 2024, Номер 327(2), С. C291 - C309

Опубликована: Июнь 3, 2024

Per- and polyfluoroalkyl substances (PFASs) are a family of "forever chemicals" including perfluorooctane sulfonate (PFOS). These toxic chemicals do not break down in the environment or our bodies. In human body, PFOS perfluoroctanoic acid (PFOA) have half-life (

Язык: Английский

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N-glycosylation of Wnt3 regulates the progression of hepatocellular carcinoma by affecting Wnt/β-catenin signal pathway

World Journal of Gastrointestinal Oncology, Год журнала: 2024, Номер 16(6), С. 2769 - 2780

Опубликована: Июнь 14, 2024

BACKGROUND Wnt/FZD-mediated signaling pathways are activated in more than 90% of hepatocellular carcinoma (HCC) cell lines. As a well-known secretory glycoprotein, Wnt3 can interact with FZD receptors on the surface, thereby activating Wnt/β-catenin pathway. However, N-glycosylation modification site and effect this biological function protein still unclear. AIM To investigate HCC cells. METHODS Site-directed mutagenesis was used to verify sites, actinomycin D treatment detect stability after site-directed mutation, binding mutant FZD7 observed by laser confocal microscopy, effects mutation pathway progression cells were detected western blot experiments. RESULTS has two N-glycosylation-modified sites (Asn90 Asn301); when single at amino acid 301 is mutated, weakened; ability decreases both mutated simultaneously; level proteins related downregulated. Cell proliferation, migration invasion also weakened case double-site mutations. CONCLUSION These results indicate that inhibiting Wnt3, migration, colony formation abilities liver cancer be weakened, which might provide new therapeutic strategies for clinical future.

Язык: Английский

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Mitoepigenetics pathways and natural compounds: a dual approach to combatting hepatocellular carcinoma

Medical Oncology, Год журнала: 2024, Номер 41(12)

Опубликована: Окт. 27, 2024

Язык: Английский

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Potentially actionable molecular alterations in particular related to poor oncologic outcomes in salivary gland carcinomas

BMC Cancer, Год журнала: 2025, Номер 25(1)

Опубликована: Янв. 8, 2025

The study was designed to evaluate molecular alterations, relevant the prognosis and personalized therapy of salivary gland cancers (SGCs). DNA extracted from archival tissue 40 patients with various SGCs subtypes. A targeted next-generation sequencing (NGS) panel used for identification small-scale mutations, focal chromosomal arm-level copy number changes. final analysis included selected genes potential actionable aberrations therapies outcome predictions in 37 tumours' samples. follow-up cohort revealed disease recurrence or metastasis 19 indicated poor individual outcomes. mean disease-free survival (DFS) within group 2.4 years, overall (OS) 5.4 years. DFS OS remaining 18 favourable outcomes were 8.3 most frequently affected NF1 (n = 9, 24%) TP53 8, 22%), increased occurrence observed group: 6, 32%) 32%). CDKN2A biallelic deletion common variation 5), detected 4 cases identified relapse. TERT promoter mutation amplification found myoepithelial carcinoma. p.Ile35Thr discovered CTNNB1 two adenoid cystic ERBB2 alterations remarkable SDC ex PA. Furthermore, established as a negative prognostic factor (p 0,04). potentially in: MECA 100% (1/1), (7/7), AD 92% (11/12), Ca PA 82% (18/22), 65% (20/31), AdCC 64% (9/14) AcCC 0% (0/1). are heterogeneous malignancies distinct landscape that characterized by inadequate treatment options. Nonstandard strategies might be beneficial who suffer cancers. Wider utilization NGS may increase opportunity those rare receive more precise, therapy.

Язык: Английский

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LARP3 inhibits the apoptosis of hepatocellular carcinoma via the ROS/PI3K/c-Fos axis

PLoS ONE, Год журнала: 2025, Номер 20(1), С. e0317454 - e0317454

Опубликована: Янв. 17, 2025

Primary hepatocellular carcinoma (PHC) is the sixth most common cancer and third leading cause of death worldwide. Hepatocellular (HCC) accounts for 75%-85% PHC. LARP3 aberrantly expressed in multiple cancers. We found that it significantly highly liver tissues HCC patients, but exact role specific mechanism this abnormal expression are not yet clear. In study, through bioinformatics analysis, we concluded associated with a poor prognosis patients HCC. Through cellular experiments such as gene editing phenotypic functions, promotes occurrence development inhibits apoptosis. Finally, biological means RNA sequencing, flow cytometry, western blotting, construction subcutaneous tumorigenesis model nude mice, inhibition apoptosis by related to negatively regulating ROS level inhibiting PI3K/c-Fos/apoptosis axis. This study will provide potential targets treatment

Язык: Английский

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