Precision treatment in advanced hepatocellular carcinoma

Cancer Cell, Год журнала: 2024, Номер 42(2), С. 180 - 197

Опубликована: Фев. 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.

Язык: Английский

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Metabolic reprogramming in the tumor microenvironment of liver cancer

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

Опубликована: Янв. 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.

Язык: Английский

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Organoids and spheroids: advanced in vitro models for liver cancer research

Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 12

Опубликована: Янв. 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

Язык: Английский

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Dual Inhibition of CDK4/6 and XPO1 Induces Senescence With Acquired Vulnerability to CRBN-Based PROTAC Drugs

Gastroenterology, Год журнала: 2024, Номер 166(6), С. 1130 - 1144.e8

Опубликована: Янв. 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

Язык: Английский

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Targeting the immune privilege of tumor-initiating cells to enhance cancer immunotherapy

Cancer Cell, Год журнала: 2024, Номер 42(12), С. 2064 - 2081.e19

Опубликована: Ноя. 7, 2024

Язык: Английский

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Integrated Lactylome Characterization Reveals the Molecular Dynamics of Protein Regulation in Gastrointestinal Cancers

Advanced Science, Год журнала: 2024, Номер unknown

Опубликована: Июль 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.

Язык: Английский

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Multidimensional Interactive Cascading Nanochips for Detection of Multiple Liver Diseases via Precise Metabolite Profiling

Advanced Materials, Год журнала: 2024, Номер 36(21)

Опубликована: Янв. 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

Язык: Английский

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Toward reproducible tumor organoid culture: focusing on primary liver cancer

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Март 20, 2024

Organoids present substantial potential for pushing forward preclinical research and personalized medicine by accurately recapitulating tissue tumor heterogeneity in vitro . However, the lack of standardized protocols cancer organoid culture has hindered reproducibility. This paper comprehensively reviews current challenges associated with highlights recent multidisciplinary advancements field a specific focus on standardizing liver culture. We discuss non-standardized aspects, including sources, processing techniques, medium formulations, matrix materials, that contribute to technical variability. Furthermore, we emphasize need establish reproducible platforms preserve genetic, proteomic, morphological, pharmacotypic features parent tumor. At end each section, our shifts standardization primary cancer. By addressing these challenges, can enhance reproducibility clinical translation systems, enabling their applications precision medicine, drug screening, research.

Язык: Английский

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Organoids: development and applications in disease models, drug discovery, precision medicine, and regenerative medicine

MedComm, Год журнала: 2024, Номер 5(10)

Опубликована: Сен. 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.

Язык: Английский

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Uncovering PROTAC Sensitivity and Efficacy by Multidimensional Proteome Profiling: A Case for STAT3

Journal of Medicinal Chemistry, Год журнала: 2024, Номер 67(6), С. 4804 - 4818

Опубликована: Март 11, 2024

Proteolysis-targeting chimera (PROTAC) is a powerful technology that can effectively trigger the degradation of target proteins. The intricate interplay among various factors leads to heterogeneous drug response, bringing about significant challenges in comprehending mechanisms. Our study applied data-independent acquisition-based mass spectrometry multidimensional proteome profiling PROTAC (DIA-MPP) uncover efficacy and sensitivity compound. We profiled signal transducer activator transcription 3 (STAT3) degrader six leukemia lymphoma cell lines under multiple conditions, demonstrating pharmacodynamic properties downstream biological responses. Through comparison between sensitive insensitive lines, we revealed STAT1 be regarded as biomarker for STAT3 degrader, which was validated cells, patient-derived organoids, mouse models. These results set an example comprehensive description response exploration.

Язык: Английский

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