Wnt/β-catenin signaling pathway in carcinogenesis and cancer therapy

Journal of Hematology & Oncology, Год журнала: 2024, Номер 17(1)

Опубликована: Июнь 18, 2024

Abstract The Wnt/β-catenin signaling pathway plays a crucial role in various physiological processes, encompassing development, tissue homeostasis, and cell proliferation. Under normal conditions, the is meticulously regulated. However, aberrant activation of this downstream target genes can occur due to mutations key components pathway, epigenetic modifications, crosstalk with other pathways. Consequently, these dysregulations contribute significantly tumor initiation progression. Therapies targeting transduction have exhibited promising prospects potential for treatment. An increasing number medications are continuously being developed validated. This comprehensive review aims summarize latest advances our understanding played by carcinogenesis targeted therapy, providing valuable insights into acknowledging current opportunities challenges associated cancer research

Язык: Английский

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Changing etiology and epidemiology of hepatocellular carcinoma: Asia and worldwide

Journal of Liver Cancer, Год журнала: 2024, Номер 24(1), С. 622 - 70

Опубликована: Март 25, 2024

Approximately 80% of hepatocellular carcinoma (HCC) cases arise in sub-Saharan Africa and Eastern Asia, following a similarly high prevalence chronic hepatitis B virus (HBV) carriers these regions. The etiology epidemiology HCC have recently changed worldwide. Although HBV infection is the main contributor to development, slow but continuous decline rates has been reported since 1990. Owing widespread use direct-acting antivirals, incidence C virus-related remarkably decreased Japan European countries. In Korea, Taiwan, Singapore, HBV-related significantly owing vaccination against HBV. Globally, while accounted for more than half HCCs 1990, this had 42% 2019. contrast, proportion patients with alcoholic- nonalcoholic steatohepatitis (NASH) increased from 13% 18% 5% 6%, respectively. NASH-related characteristics that differ those virus-associated HCC. Compared other etiologies, NASHassociated are older, higher body mass index, type 2 diabetes mellitus, hypertension, hyperlipidemia, cardiovascular disease. Nonalcoholic fatty liver disease (NAFLD)-associated also known develop absence cirrhosis, unlike alcohol-related autoimmune diseases. Because NAFLD usually or obesity, surveying population challenging. Optimal selection target surveillance tools among needs be determined.

Язык: Английский

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Biomarkers for diagnosis and therapeutic options in hepatocellular carcinoma

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Сен. 6, 2024

Язык: Английский

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N6-Methyladenosine Reader YTHDF1 Promotes Stemness and Therapeutic Resistance in Hepatocellular Carcinoma by Enhancing NOTCH1 Expression

Cancer Research, Год журнала: 2024, Номер 84(6), С. 827 - 840

Опубликована: Янв. 19, 2024

Abstract N6-methyladenosine (m6A) RNA modification is the most common and conserved epigenetic in mRNA has been shown to play important roles cancer biology. As m6A reader YTHDF1 reported promote progression of hepatocellular carcinoma (HCC), it represents a potential therapeutic target. In this study, we evaluated clinical significance using human HCC samples found that was significantly upregulated HCCs with high stemness scores positively associated recurrence poor prognosis. Analysis spheroids revealed highly expressed liver stem cells (CSC). Stem cell–specific conditional Ythdf1 knockin (CKI) mice treated diethylnitrosamine showed elevated tumor burden as compared wild-type mice. promoted CSCs renewal resistance multiple tyrosine kinase inhibitors lenvatinib sorafenib patient-derived organoids cell lines, which could be abolished by catalytically inactive mutant YTHDF1. Multiomic analysis, including immunoprecipitation sequencing, methylated ribosome profiling, sequencing identified NOTCH1 direct downstream bound modified enhance its stability translation, led increased target genes expression. overexpression rescued YTHDF1-deficient vitro vivo. Lipid nanoparticles targeting enhanced efficacy Taken together, drives drug through an YTHDF1–m6A–NOTCH1 epitranscriptomic axis, for treating HCC. Significance: Inhibition expression suppresses enhances sensitivity targeted therapies, indicating may promising strategy cancer.

Язык: Английский

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Disulfidptosis-related lncRNA signatures assess immune microenvironment and drug sensitivity in hepatocellular carcinoma

Computers in Biology and Medicine, Год журнала: 2024, Номер 169, С. 107930 - 107930

Опубликована: Янв. 4, 2024

Язык: Английский

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Liver diseases: epidemiology, causes, trends and predictions

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

Опубликована: Фев. 4, 2025

Abstract As a highly complex organ with digestive, endocrine, and immune-regulatory functions, the liver is pivotal in maintaining physiological homeostasis through its roles metabolism, detoxification, immune response. Various factors including viruses, alcohol, metabolites, toxins, other pathogenic agents can compromise function, leading to acute or chronic injury that may progress end-stage diseases. While sharing common features, diseases exhibit distinct pathophysiological, clinical, therapeutic profiles. Currently, contribute approximately 2 million deaths globally each year, imposing significant economic social burdens worldwide. However, there no cure for many kinds of diseases, partly due lack thorough understanding development these Therefore, this review provides comprehensive examination epidemiology characteristics covering spectrum from conditions manifestations. We also highlight multifaceted mechanisms underlying initiation progression spanning molecular cellular levels networks. Additionally, offers updates on innovative diagnostic techniques, current treatments, potential targets presently under clinical evaluation. Recent advances pathogenesis hold critical implications translational value novel strategies.

Язык: Английский

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circCCNY enhances lenvatinib sensitivity and suppresses immune evasion in hepatocellular carcinoma by serving as a scaffold for SMURF1 mediated HSP60 degradation

Cancer Letters, Год журнала: 2025, Номер 612, С. 217470 - 217470

Опубликована: Янв. 17, 2025

Язык: Английский

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Clinical Applications of Artificial Intelligence (AI) in Human Cancer: Is It Time to Update the Diagnostic and Predictive Models in Managing Hepatocellular Carcinoma (HCC)?

Diagnostics, Год журнала: 2025, Номер 15(3), С. 252 - 252

Опубликована: Янв. 22, 2025

In recent years, novel findings have progressively and promisingly supported the potential role of Artificial intelligence (AI) in transforming management various neoplasms, including hepatocellular carcinoma (HCC). HCC represents most common primary liver cancer. Alarmingly, incidence is dramatically increasing worldwide due to simultaneous “pandemic” spreading metabolic dysfunction-associated steatotic disease (MASLD). MASLD currently constitutes leading cause chronic hepatic damage (steatosis steatohepatitis), fibrosis, cirrhosis, configuring a scenario where an onset has been reported even early stage. On other hand, serious plague, significantly burdening outcomes hepatitis B (HBV) C (HCV) virus-infected patients. Despite progress this cancer, overall prognosis for advanced-stage patients continues be poor, suggesting absolute need develop personalized healthcare strategies further. “cold war”, machine learning techniques neural networks are emerging as weapons, able identify patterns biomarkers that would normally escaped human observation. Using advanced algorithms, AI can analyze large volumes clinical data medical images (including routinely obtained ultrasound data) with elevated accuracy, facilitating diagnosis, improving performance predictive models, supporting multidisciplinary (oncologist, gastroenterologist, surgeon, radiologist) team opting best “tailored” individual treatment. Additionally, contribute enhancing effectiveness metabolomics–radiomics-based promoting identification specific HCC-pathogenetic molecules new targets realizing therapeutic regimens. era precision medicine, integrating into routine practice appears promising frontier, opening avenues cancer research

Язык: Английский

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Hepatocellular carcinoma

European Journal of Surgical Oncology, Год журнала: 2023, Номер 50(1), С. 107313 - 107313

Опубликована: Дек. 6, 2023

Язык: Английский

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PTTG1 Reprograms Asparagine Metabolism to Promote Hepatocellular Carcinoma Progression

Cancer Research, Год журнала: 2023, Номер 83(14), С. 2372 - 2386

Опубликована: Май 9, 2023

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and has a poor prognosis. Pituitary tumor transforming gene 1 (PTTG1) highly expressed in HCC, suggesting it could play an important role hepatocellular carcinogenesis. Here, we evaluated impact PTTG1 deficiency on HCC development using diethylnitrosamine (DEN)-induced mouse model hepatitis B virus (HBV) regulatory X protein (HBx)-induced spontaneous model. significantly suppressed DEN- HBx-induced Mechanistically, promoted asparagine synthetase (ASNS) transcription by binding to its promoter, (Asn) levels were correspondingly increased. The elevated Asn subsequently activated mTOR pathway facilitate progression. In addition, asparaginase treatment reversed proliferation induced overexpression. Furthermore, HBx ASNS metabolism upregulating expression. Overall, involved reprogramming promote progression may serve as therapeutic diagnostic target for HCC.PTTG1 upregulated increases production stimulate activity

Язык: Английский

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