Hepatocellular carcinoma: signaling pathways and therapeutic advances

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Фев. 6, 2025

Abstract Liver cancer represents a major global health concern, with projections indicating that the number of new cases could surpass 1 million annually by 2025. Hepatocellular carcinoma (HCC) constitutes around 90% liver and is primarily linked to factors incluidng aflatoxin, hepatitis B (HBV) C (HCV), metabolic disorders. There are no obvious symptoms in early stage HCC, which often leads delays diagnosis. Therefore, HCC patients usually present tumors advanced incurable stages. Several signaling pathways dis-regulated cause uncontrolled cell propagation, metastasis, recurrence HCC. Beyond frequently altered therapeutically targeted receptor tyrosine kinase (RTK) involved differentiation, telomere regulation, epigenetic modification stress response also provide therapeutic potential. Investigating key their inhibitors pivotal for achieving advancements management At present, primary approaches (TKI), immune checkpoint (ICI), combination regimens. New trials investigating therapies involving ICIs TKIs or anti-VEGF (endothelial growth factor) therapies, as well combinations two immunotherapy The outcomes these expected revolutionize across all Here, we here comprehensive review cellular pathways, potential, evidence derived from late-stage clinical discuss concepts underlying earlier trials, biomarker identification, development more effective therapeutics

Язык: Английский

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Modern biology of extrachromosomal DNA: A decade-long voyage of discovery

Cell Research, Год журнала: 2025, Номер 35(1), С. 11 - 22

Опубликована: Янв. 3, 2025

Abstract Genomic instability is a hallmark of cancer and major driving force tumorigenesis. A key manifestation genomic the formation extrachromosomal DNAs (ecDNAs) — acentric, circular DNA molecules ranging from 50 kb to 5 Mb in size, distinct chromosomes. Ontological studies have revealed that ecDNA serves as carrier oncogenes, immunoregulatory genes, enhancers, capable elevated transcription its cargo genes heterogeneity, leading rapid tumor evolution therapy resistance. Although was documented over half century ago, past decade has witnessed surge breakthrough discoveries about biological functions. Here, we systematically review modern biology uncovered last ten years, focusing on how during this pioneering stage illuminated our understanding ecDNA-driven transcription, progression. Furthermore, discuss ongoing efforts target novel approach therapy. This burgeoning field entering new phase, poised reshape knowledge therapeutic strategies.

Язык: Английский

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Hepatocellular Carcinoma: Current Drug Therapeutic Status, Advances and Challenges

Cancers, Год журнала: 2024, Номер 16(8), С. 1582 - 1582

Опубликована: Апрель 20, 2024

Hepatocellular carcinoma (HCC) is the most common form of liver cancer, accounting for ~90% neoplasms. It second leading cause cancer-related deaths and seventh cancer worldwide. Although there have been rapid developments in treatment HCC over past decade, incidence mortality rates remain a challenge. With widespread use hepatitis B vaccine antiviral therapy, etiology shifting more toward metabolic-associated steatohepatitis (MASH). Early-stage can be treated with potentially curative strategies such as surgical resection, transplantation, radiofrequency ablation, improving long-term survival. However, patients, when diagnosed, are already intermediate or advanced stages. Molecular targeted followed by immune checkpoint inhibitor immunotherapy, has revolution systemic treatment. Systemic especially patients compromised function still challenge due to significant resistance blockade, tumor heterogeneity, lack oncogenic addiction, effective predictive therapeutic biomarkers.

Язык: Английский

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Hepatitis Delta Virus and Hepatocellular Carcinoma

Pathogens, Год журнала: 2024, Номер 13(5), С. 362 - 362

Опубликована: Апрель 27, 2024

The hepatitis D virus (HDV) is a compact, enveloped, circular RNA that relies on B (HBV) envelope proteins to initiate primary infection in hepatocytes, assemble, and secrete new virions. Globally, HDV affects an estimated 12 million 72 people, carrying significantly elevated risk of developing cirrhosis, liver failure, hepatocellular carcinoma (HCC) compared HBV mono-infection. Furthermore, HDV-associated HCC often manifests at younger age exhibits more aggressive characteristics. intricate mechanisms driving the synergistic carcinogenicity are not fully elucidated but believed involve chronic inflammation, immune dysregulation, direct oncogenic effects HDV. Indeed, recent data highlight molecular profile associated with unique distinct from HBV-induced HCC. However, question whether remains unanswered. In this review, we comprehensively examined several crucial aspects HDV, encompassing its epidemiology, biology, immunology, risks disease progression development.

Язык: Английский

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Fibrinogen and tumors

Frontiers in Oncology, Год журнала: 2024, Номер 14

Опубликована: Май 8, 2024

Elevated plasma fibrinogen (Fg) levels consistently correlate with an unfavorable prognosis in various tumor patient cohorts. Within the microenvironment, aberrant deposition and expression of Fg have been observed, interacting multiple cellular receptors thereby accentuating its role as a regulator inflammatory processes. Specifically, serves to stimulate recruit immune cells pro-inflammatory cytokines, contributing promotion progression. Additionally, fragments exhibit dichotomous effects on angiogenesis. Notably, also facilitates migration through both platelet-dependent platelet-independent mechanisms. Recent studies illuminated several tumor-related signaling pathways influenced by Fg. This review provides comprehensive summary intricate involvement biology, elucidating multifaceted underlying

Язык: Английский

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Should AI-Powered Whole-Genome Sequencing Be Used Routinely for Personalized Decision Support in Surgical Oncology—A Scoping Review

BioMedInformatics, Год журнала: 2024, Номер 4(3), С. 1757 - 1772

Опубликована: Июль 24, 2024

In this scoping review, we delve into the transformative potential of artificial intelligence (AI) in addressing challenges inherent whole-genome sequencing (WGS) analysis, with a specific focus on its implications oncology. Unveiling limitations existing technologies, review illuminates how AI-powered methods emerge as innovative solutions to surmount these obstacles. The evolution DNA progressing from Sanger next-generation sequencing, sets backdrop for AI’s emergence potent ally processing and analyzing voluminous genomic data generated. Particularly, deep learning play pivotal role extracting knowledge discerning patterns vast landscape information. context oncology, exhibit considerable across diverse facets WGS including variant calling, structural variation identification, pharmacogenomic analysis. This underscores significance multimodal approaches diagnoses therapies, highlighting importance ongoing research development techniques. Integrating AI analytical framework empowers scientists clinicians unravel intricate interplay genomics within realm multi-omics research, paving way more successful personalized targeted treatments.

Язык: Английский

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Investigating the origins of the mutational signatures in cancer

Nucleic Acids Research, Год журнала: 2025, Номер 53(1)

Опубликована: Янв. 7, 2025

Abstract Most of the risk factors associated with chronic and complex diseases, such as cancer, stem from exogenous endogenous exposures experienced throughout an individual’s life, collectively known exposome. These can modify DNA, which subsequently lead to somatic mutations found in all normal tumor tissues. Understanding precise origins specific has been challenging due multitude DNA adducts (i.e. adductome) their diverse positions within genome. Thus far, this limitation prevented researchers precisely linking subsequent mutational outcomes. Indeed, many common observed human cancers appear originate error-prone processes. Consequently, it remains unclear whether these result exposure-induced adducts, or arise indirectly processes are a combination both. In review, we summarize approaches that aim bridge our understanding mechanism by exposure leads damage then mutation highlight some remaining challenges shortcomings fully supporting paradigm. We emphasize need integrate cellular adductomics, long read-based mapping, single-molecule duplex sequencing native molecules advanced computational analysis. This proposed holistic approach aims unveil causal connections between key modifications landscape, they external exposures, internal both, thereby addressing questions cancer biology.

Язык: Английский

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An expanding universe of mutational signatures and its rapid evolution in single-stranded RNA viruses

Molecular Biology and Evolution, Год журнала: 2025, Номер unknown

Опубликована: Янв. 17, 2025

Abstract The study of mutational processes in somatic genomes has gained recent momentum, uncovering a wide array endogenous and exogenous factors associated with changes. However, the overall landscape germline mutations across tree life evolutionary driving forces are rather unclear. In this study, we analyzed single-stranded RNA (ssRNA) viruses which known to jump between different hosts divergent environments. We found that spectra ssRNA differ significantly mainly their genetic divergence. Surprisingly, host environments contribute much less spectrum, challenging prevailing view cellular environment is major determinant spectrum viruses. To dissect shaping viral spectra, selected two important scenarios, namely inter-host evolution strains as well intra-host evolution. both change through space time, strongly correlating levels natural selection. Combining all viruses, identified suite signatures varying degrees similarity humans, indicating universal life. Taken together, unraveled an unprecedented dynamic pinpointing fast species.

Язык: Английский

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Sorafenib as Adjuvant Therapy Post–Liver Transplant: A Single-center Experience

Transplantation Direct, Год журнала: 2025, Номер 11(2), С. e1746 - e1746

Опубликована: Янв. 23, 2025

Background. Hepatocellular carcinoma (HCC) has a rising incidence and mortality in North America. Liver transplantation (LT) with adjunctive therapies offers excellent outcomes. However, HCC recurrences are associated high mortality. We investigate whether adjuvant systemic therapy can reduce recurrence, as shown other malignancies. Methods. Medical records of patients undergoing LT for at single center between January 2016 December 2022 were retrospectively reviewed. Patients stratified into 3 groups: (1) recipients sorafenib, (2) nonrecipients recurrence risk, (3) low risk by explant pathology features. The outcomes overall survival (OS) recurrence-free (RFS). Adjuvant sorafenib also propensity score matched 1:2 to nonadjuvant based on Results. During the study period, 273 underwent 16 (5.9%) received therapy. demographically similar and, pathology, had greater tumor burden, lymphovascular invasion, poorer differentiation (all P < 0.001). Adverse events observed 12 (75%). OS was among groups ( = 0.2), not multivariable analysis (hazard ratio, 1.31; 95% confidence interval, 0.45-3.78; 0.62). RFS significantly lower 6.99; 2.12-23.05; Following matching, use either 0.24) or rates 0.65). Conclusions. In this single-center analysis, OS. Recipients have shorter RFS, likely due increased prevalence high-risk features, frequencies adverse events.

Язык: Английский

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Pifithrin-μ sensitizes mTOR-activated liver cancer to sorafenib treatment

Cell Death and Disease, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 26, 2025

Язык: Английский

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