Digestive cancers: mechanisms, therapeutics and management

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 14, 2025

Abstract Cancers of the digestive system are major contributors to global cancer-associated morbidity and mortality, accounting for 35% annual cases cancer deaths. The etiologies, molecular features, therapeutic management these entities highly heterogeneous complex. Over last decade, genomic functional studies have provided unprecedented insights into biology cancers, identifying genetic drivers tumor progression key interaction points cells with immune system. This knowledge is continuously translated novel treatment concepts targets, which dynamically reshaping landscape tumors. In this review, we provide a concise overview etiology pathology six most common cancers system, including esophageal, gastric, biliary tract, pancreatic, hepatocellular, colorectal cancers. We comprehensively describe current stage-dependent pharmacological malignancies, chemo-, targeted, immunotherapy. For each entity, an recent advancements research progress. Finally, how heterogeneity evasion deepen our understanding therapy resistance outlook on innovative strategies that will shape future CAR-T cell therapy, antibody-drug conjugates targeted therapies.

Language: Английский

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Epidemiologic, Genetic, Pathogenic, Metabolic, Epigenetic Aspects Involved in NASH-HCC: Current Therapeutic Strategies

Cancers, Journal Year: 2022, Volume and Issue: 15(1), P. 23 - 23

Published: Dec. 20, 2022

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and sixth frequent in world, being third cause of cancer-related deaths. Nonalcoholic steatohepatitis (NASH) characterized by fatty infiltration, oxidative stress necroinflammation liver, with or without fibrosis, which can progress to advanced cirrhosis HCC. Obesity, metabolic syndrome, insulin resistance, diabetes exacerbates course NASH, elevate risk The growing prevalence obesity are related increasing incidence may play a role HCC epidemiology worldwide. In addition, initiation progression driven reprogramming metabolism, indicates appreciation metabolism pathogenesis this disease. Although no specific preventive pharmacological treatments have recommended for dietary restriction exercise recommended. This review focuses on molecular connections between including genetic factors, highlighting aberrant epigenetic alterations development NASH. Current therapeutic aspects NASH/HCC also reviewed.

Language: Английский

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Exosome-derived circUPF2 enhances resistance to targeted therapy by redeploying ferroptosis sensitivity in hepatocellular carcinoma

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

Published: May 30, 2024

Abstract Background Advanced hepatocellular carcinoma (HCC) can be treated with sorafenib, which is the primary choice for targeted therapy. Nevertheless, effectiveness of sorafenib greatly restricted due to resistance. Research has shown that exosomes and circular RNAs play a vital role in cancer’s malignant advancement. However, significance exosomal development resistance HCC remains uncertain. Methods Ultracentrifugation was utilized isolate (Exo-SR) from sorafenib-resistant cells’ culture medium. Transcriptome sequencing differential expression gene analysis were used identify targets Exo-SR action cells. To cells, transcriptome genes employed. evaluate impact circUPF2 on HCC, experiments involving gain-of-function loss-of-function conducted. RNA pull-down assays mass spectrometry performed RNA-binding proteins interacting circUPF2. immunoprecipitation (RIP), pull-down, electrophoretic mobility shift assay (EMSA), immunofluorescence (IF) -fluorescence situ hybridization (FISH), rescue validate interactions among circUPF2, IGF2BP2 SLC7A11. Finally, tumor xenograft examine biological functions underlying mechanisms vivo. Results A novel circRNA, identified revealed significantly enriched Exo-SR. Exosomes enhanced by promoting SLC7A11 suppressing ferroptosis Mechanistically, acts as framework enhance creation circUPF2-IGF2BP2-SLC7A11 ternary complex contributing stabilization mRNA. Consequently, promotes enhances function system Xc- leading decreased sensitivity sorafenib. Conclusions The facilitated formation increases stability Focusing could potentially an innovative approach treatment. Graphical

Language: Английский

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Translational research on drug development and biomarker discovery for hepatocellular carcinoma

Journal of Biomedical Science, Journal Year: 2024, Volume and Issue: 31(1)

Published: Feb. 17, 2024

Abstract Translational research plays a key role in drug development and biomarker discovery for hepatocellular carcinoma (HCC). However, unique challenges exist this field because of the limited availability human tumor samples from surgery, lack homogenous oncogenic driver mutations, paucity adequate experimental models. In review, we provide insights into these review recent advancements, with particular focus on two main agents currently used as mainstream therapies HCC: anti-angiogenic immunotherapy. First, examine pre-clinical clinical studies to highlight determining optimal therapeutic combinations biologically effective dosage HCC. Second, discuss focusing anti-PD1/anti-PD-L1-based combination therapy. Finally, progress made our collective understanding immunology multi-omics analysis technology, which enhance mechanisms underlying immunotherapy, characterize different patient subgroups, facilitate novel approaches improve treatment efficacy. summary, provides comprehensive overview efforts translational aiming at advancing improving

Language: Английский

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Long Noncoding RNA H19: A Novel Oncogene in Liver Cancer

Non-Coding RNA, Journal Year: 2023, Volume and Issue: 9(2), P. 19 - 19

Published: March 9, 2023

Liver cancer is the second leading cause of cancer-related death globally, with limited treatment options. Recent studies have demonstrated critical role long noncoding RNAs (lncRNAs) in pathogenesis liver cancers. Of note, mounting evidence has shown that lncRNA H19, an endogenous single-stranded RNA, functions as oncogene development and progression cancer, including hepatocellular carcinoma (HCC) cholangiocarcinoma (CCA), two most prevalent primary tumors adults. H19 can affect many biological processes, cell proliferation, apoptosis, invasion, metastasis by its function on epigenetic modification, H19/miR-675 axis, miRNAs sponge, drug resistance, regulation downstream pathways. In this review, we will focus relevant molecular mechanisms action pathophysiology HCC CCA. This review aims to provide valuable perspectives translational applications a potential diagnostic marker therapeutic target for disease.

Language: Английский

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The role of RNA modification in hepatocellular carcinoma

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 2, 2022

Hepatocellular carcinoma (HCC) is a highly mortal type of primary liver cancer. Abnormal epigenetic modifications are present in HCC, and RNA modification dynamic reversible key post-transcriptional regulator. With the in-depth study modifications, aberrantly expressed human cancers. Moreover, regulators can be used as potential targets for cancer therapy. In N6-methyladenosine (m6A), N7-methylguanosine (m7G), 5-methylcytosine (m5C) their have important regulatory roles HCC progression represent novel biomarkers confirmation diagnosis treatment HCC. This review focuses on mechanisms m6A, m7G, m5C, N1-methyladenosine (m1A), N3-methylcytosine (m3C), pseudouridine (ψ) its development maintenance. The therapeutic strategies elaborated

Language: Английский

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Old age as a risk factor for liver diseases: Modern therapeutic approaches

Experimental Gerontology, Journal Year: 2023, Volume and Issue: 184, P. 112334 - 112334

Published: Nov. 25, 2023

Recent scientific interest has been directed towards age-related diseases, driven by the significant increase in global life expectancy and growing population of individuals aged 65 above. The ageing process encompasses various biological, physiological, environmental, psychological, behavioural, social changes, leading to an augmented susceptibility chronic illnesses. Cardiovascular, neurological, musculoskeletal, liver oncological diseases are prevalent elderly. Moreover, demonstrate reduced regenerative capacity decreased tolerance therapeutic interventions, including organ transplantation. Liver such as non-alcoholic fatty disease, alcoholic hepatitis, fibrosis, cirrhosis, have emerged public health concerns. Paradoxically, these conditions remain underestimated despite their substantial impact. Age-related factors closely associated with severity unfavorable prognosis warranting further investigation enhance clinical management develop novel strategies. This comprehensive review focuses specifically on treatment strategies, contemporary practices. It provides a detailed account burden, types, molecular mechanisms, epigenetic alterations underlying pathologies.

Language: Английский

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EPS15-AS1 Inhibits AKR1B1 Expression to Enhance Ferroptosis in Hepatocellular Carcinoma Cells

Journal of Cancer, Journal Year: 2024, Volume and Issue: 15(4), P. 1030 - 1040

Published: Jan. 1, 2024

Epidermal growth factor receptor substrate 15 (EPS15) is part of the EGFR pathway and has been implicated in various tumorigenesis.Increasing evidence suggests that long noncoding RNA (lncRNA) plays an essential role liver hepatocellular carcinoma (LIHC) by regulating expression proteins genes.Through analysis cancer genome atlas (TCGA) database, we found EPS15 highly expressed LIHC tissue, lncRNA EPS15-antisense1 (EPS15-AS1) decreased cell lines.However, function EPS15-AS1 still unknown.When was overexpressed HepG2 lines, reduced activity invasiveness were inhibited.In addition, observed increase Fe 2+ ion lipid peroxidation after overexpression EPS15-AS1, further showed susceptibility to ferroptosis increased.Aldo-keto reductase family 1 member B (AKR1B1) belongs aldo/keto superfamily involved maintaining cellular redox balance.Survival revealed patients with a higher level AKR1B1 have lower survival rate TCGA database.We also enhanced LIHC, had ability promote invasiveness.Moreover, alleviated promoting effect on ferroptosis.Therefore, can induce cells inhibiting disrupting balance.EPS15 may serve as biomarkers for diagnosis potential drug LIHC.

Language: Английский

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Crosstalk between Epigenetics and Metabolic Reprogramming in Metabolic Dysfunction-Associated Steatotic Liver Disease-Induced Hepatocellular Carcinoma: A New Sight

Metabolites, Journal Year: 2024, Volume and Issue: 14(6), P. 325 - 325

Published: June 8, 2024

Epigenetic and metabolic reprogramming alterations are two important features of tumors, their reversible, spatial, temporal regulation is a distinctive hallmark carcinogenesis. Epigenetics, which focuses on gene regulatory mechanisms beyond the DNA sequence, new entry point for tumor therapy. Moreover, drives hepatocellular carcinoma (HCC) initiation progression, highlighting significance metabolism in this disease. Exploring inter-regulatory relationship between epigenetic modification has become one hot directions current research. As viral etiologies have given way to dysfunction-associated steatotic liver disease (MASLD)-induced HCC, it urgent that complex molecular pathways linking them hepatocarcinogenesis be explored. However, how aberrant crosstalk modifications affects MASLD-induced HCC lacks comprehensive understanding. A better understanding linkages necessary improve treatment strategies. For reason, review examines interwoven landscape carcinogenesis context focusing regulating development interactions while also updating advances modification-based therapeutic drugs HCC.

Language: Английский

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A new strategy for overcoming drug resistance in liver cancer: Epigenetic regulation

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 176, P. 116902 - 116902

Published: June 12, 2024

Drug resistance in hepatocellular carcinoma has posed significant obstacles to effective treatment. Recent evidence indicates that, addition traditional gene mutations, epigenetic recoding plays a crucial role HCC drug resistance. Unlike irreversible changes are reversible, offering promising avenue for preventing and overcoming liver cancer. This review focuses on various modifications relevant their underlying mechanisms. Additionally, we introduce current clinical drugs trials of these as regulators other solid tumors. Although there is no study prevent the occurrence cancer, development liquid biopsy technologies provided bridge achieve this goal.

Language: Английский

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