Cancer Cell, Journal Year: 2024, Volume and Issue: 42(2), P. 180 - 197
Published: Feb. 1, 2024
The past decade has witnessed significant advances in the systemic treatment of advanced hepatocellular carcinoma (HCC). Nevertheless, newly developed strategies have not achieved universal success and HCC patients frequently exhibit therapeutic resistance to these therapies. Precision represents a paradigm shift cancer recent years. This approach utilizes unique molecular characteristics individual patient personalize modalities, aiming maximize efficacy while minimizing side effects. Although precision shown multiple types, its application remains infancy. In this review, we discuss key aspects HCC, including biomarkers, classifications, heterogeneity tumor microenvironment. We also propose future directions, ranging from revolutionizing current methodologies personalizing therapy through functional assays, which will accelerate next phase advancements area.
Language: Английский
Citations
124Metabolic reprogramming in the tumor microenvironment of liver cancer
Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)
Published: Jan. 31, 2024
The liver is essential for metabolic homeostasis. onset of cancer often accompanied by dysregulated function, leading to rearrangements. Overwhelming evidence has illustrated that cellular metabolism can, in turn, promote anabolic growth and tumor propagation a hostile microenvironment. In addition supporting continuous survival, disrupted process also creates obstacles the anticancer immune response restrains durable clinical remission following immunotherapy. this review, we elucidate communication between cells their surrounding discuss how reprogramming impacts microenvironment efficacy We describe crucial role gut-liver axis remodeling crosstalk surveillance escape, highlighting novel therapeutic opportunities.
Language: Английский
Citations
41Dual Inhibition of CDK4/6 and XPO1 Induces Senescence With Acquired Vulnerability to CRBN-Based PROTAC Drugs
Gastroenterology, Journal Year: 2024, Volume and Issue: 166(6), P. 1130 - 1144.e8
Published: Jan. 21, 2024
Background & AimsDespite the increasing number of treatment options available for liver cancer, only a small proportion patients achieve long-term clinical benefits. Here, we aim to develop new therapeutic approaches cancer.MethodsA compound screen was conducted identify inhibitors that could synergistically induce senescence when combined with cyclin-dependent kinase (CDK) 4/6 inhibitor. The combination effects CDK4/6 inhibitor and exportin 1 (XPO1) on cellular were investigated in panel human cancer cell lines multiple models. A senolytic drug performed drugs selectively killed senescent cells.ResultsThe XPO1 induces cells vitro vivo. acts by causing accumulation RB1 nucleus, leading decreased E2F signaling promoting induction Through screen, cereblon (CRBN)–based proteolysis targeting chimera (PROTAC) ARV-825 identified as an agent can kill cells. Up-regulation CRBN vulnerability cells, making them sensitive CRBN-based PROTAC drugs. Mechanistically, find ubiquitin carboxyl-terminal hydrolase 2 (USP2) directly interacts CRBN, deubiquitination stabilization cells.ConclusionsOur study demonstrates striking synergy through These findings also shed light molecular processes underlying therapy. Despite cancer. Our
Language: Английский
Citations
17Targeting the immune privilege of tumor-initiating cells to enhance cancer immunotherapy
Cancer Cell, Journal Year: 2024, Volume and Issue: 42(12), P. 2064 - 2081.e19
Published: Nov. 7, 2024
Language: Английский
Citations
13Multidimensional Interactive Cascading Nanochips for Detection of Multiple Liver Diseases via Precise Metabolite Profiling
Advanced Materials, Journal Year: 2024, Volume and Issue: 36(21)
Published: Jan. 24, 2024
Abstract It is challenging to detect and differentiate multiple diseases with high complexity/similarity from the same organ. Metabolic analysis based on nanomatrix‐assisted laser desorption/ionization mass spectrometry (NMALDI‐MS) a promising platform for disease diagnosis, while enhanced property of its core nanomatrix materials has plenty room improvement. Herein, multidimensional interactive cascade nanochip composed iron oxide nanoparticles (FeNPs)/MXene/gold (AuNPs), IMG, reported serum metabolic profiling achieve high‐throughput detection liver diseases. MXene serves as multi‐binding site an electron‐hole source ionization during NMALDI‐MS analysis. Introduction AuNPs surface plasmon resonance (SPR) properties facilitates charge accumulation rapid energy conversion. FeNPs are integrated into MXene/Au nanocomposite sharply reduce thermal conductivity negligible heat loss strong thermally‐driven desorption, construct multi‐interaction proton transport pathway ionization. Analysis these fingerprint signals detected IMG through neural network model results in differentiation via single pass revelation potential biomarkers. The method can rapidly accurately screen various diseases, thus allowing timely treatment
Language: Английский
Citations
10Integrated Lactylome Characterization Reveals the Molecular Dynamics of Protein Regulation in Gastrointestinal Cancers
Advanced Science, Journal Year: 2024, Volume and Issue: unknown
Published: July 17, 2024
Lysine lactylation (Kla) plays a vital role in several physiological processes. However, the cancer-specific modulation of Kla gastrointestinal (GI) tumors requires systematic elucidation. Here, global lactylome profiling cancerous and adjacent tissues is conducted from 40 patients with GI cancer identified 11698 sites. Lactylome integration revealed that affects proteins involved hallmark processes, including epigenetic rewiring, metabolic perturbations, genome instability. Moreover, study pan-cancer patterns alterations, among which 37 sites are consistently upregulated all four cancers gene regulation. It further verified CBX3 at K10 mediates its interaction marker H3K9me3 facilitates progression. Overall, this provides an invaluable resource for understanding landscape cancers, may provide new paths drug discovery these devastating diseases.
Language: Английский
Citations
10Organoids and spheroids: advanced in vitro models for liver cancer research
Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 12
Published: Jan. 9, 2025
Liver cancer is a leading cause of cancer-related deaths worldwide, highlighting the need for innovative approaches to understand its complex biology and develop effective treatments. While traditional in vivo animal models have played vital role liver research, ethical concerns demand more human-relevant systems driven development advanced vitro models. Spheroids organoids emerged as powerful tools due their ability replicate tumor microenvironment facilitate preclinical drug development. are simpler 3D culture that partially recreate structure cell interactions. They can be used penetration studies high-throughput screening. Organoids derived from stem cells or patient tissues accurately emulate complexity functionality tissue. generated pluripotent adult cells, well specimens, providing personalized studying behavior responses. retain genetic variability original offer robust platform screening treatment strategies. However, both spheroids limitations, such absence functional vasculature immune components, which essential growth therapeutic The field modeling evolving, with ongoing efforts predictive reflect complexities human cancer. By integrating these tools, researchers gain deeper insights into accelerate novel
Language: Английский
Citations
1DYRK1A-TGF-β signaling axis determines sensitivity to OXPHOS inhibition in hepatocellular carcinoma
Developmental Cell, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 1, 2025
Language: Английский
Citations
1Recent progress on the organoids: Techniques, advantages and applications
Biomedicine & Pharmacotherapy, Journal Year: 2025, Volume and Issue: 185, P. 117942 - 117942
Published: March 4, 2025
Language: Английский
Citations
1Organoids: development and applications in disease models, drug discovery, precision medicine, and regenerative medicine
MedComm, Journal Year: 2024, Volume and Issue: 5(10)
Published: Sept. 21, 2024
Organoids are miniature, highly accurate representations of organs that capture the structure and unique functions specific organs. Although field organoids has experienced exponential growth, driven by advances in artificial intelligence, gene editing, bioinstrumentation, a comprehensive overview organoid applications remains necessary. This review offers detailed exploration historical origins characteristics various types, their applications-including disease modeling, drug toxicity efficacy assessments, precision medicine, regenerative medicine-as well as current challenges future directions research. have proven instrumental elucidating genetic cell fate hereditary diseases, infectious metabolic disorders, malignancies, study processes such embryonic development, molecular mechanisms, host-microbe interactions. Furthermore, integration technology with intelligence microfluidics significantly advanced large-scale, rapid, cost-effective thereby propelling progress medicine. Finally, advent high-performance materials, three-dimensional printing technology, also gaining prominence Our insights predictions aim to provide valuable guidance researchers support continued advancement this rapidly developing field.
Language: Английский
Citations
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