Neoplasia, Год журнала: 2024, Номер 58, С. 101076 - 101076
Опубликована: Окт. 31, 2024
Язык: Английский
Molecular Cancer, Год журнала: 2025, Номер 24(1)
Опубликована: Янв. 11, 2025
The Kirsten rat sarcoma viral oncogene homolog (KRAS) protein plays a key pathogenic role in oncogenesis, cancer progression, and metastasis. Numerous studies have explored the of metabolic alterations KRAS-driven cancers, providing scientific rationale for targeting metabolism treatment. development KRAS-specific inhibitors has also garnered considerable attention, partly due to challenge acquired treatment resistance. Here, we review reprogramming glucose, glutamine, lipids regulated by oncogenic KRAS, with an emphasis on recent insights into relationship between changes mechanisms driven KRAS mutant related advances targeted therapy. We focus inhibitor discovery strategies colorectal, pancreatic, non-small cell lung cancer, including current clinical trials. Therefore, this provides overview understanding associated mutation therapeutic strategies, aiming facilitate challenges support investigation strategies.
Язык: Английский
Процитировано
4
Advanced Healthcare Materials, Год журнала: 2024, Номер 13(22)
Опубликована: Май 16, 2024
Abstract Chemodynamic therapy (CDT) has emerged as a transformative paradigm in the realm of reactive oxygen species ‐mediated cancer therapies, exhibiting its potential sophisticated strategy for precise and effective tumor treatment. CDT primarily relies on metal ions hydrogen peroxide to initiate Fenton or Fenton‐like reactions, generating cytotoxic hydroxyl radicals. Its notable advantages treatment are demonstrated, including specificity, autonomy from external triggers, favorable side‐effect profile. Recent advancements nanomedicine devoted enhancing CDT, promising comprehensive optimization efficacy. This review systematically elucidates cutting‐edge achievements chemodynamic nanotherapeutics, exploring strategies enhanced improved microenvironment modulation, regulation energy metabolism. Moreover, detailed analysis diverse CDT‐mediated combination therapies is provided. Finally, concludes with discussion prospects intrinsic challenges application nanotherapeutics domain
Язык: Английский
Процитировано
15
Cellular Signalling, Год журнала: 2024, Номер 120, С. 111239 - 111239
Опубликована: Май 28, 2024
Язык: Английский
Процитировано
13
Experimental Hematology and Oncology, Год журнала: 2024, Номер 13(1)
Опубликована: Апрель 23, 2024
Abstract The interaction between programmed cell death ligand 1 (PD-L1), which is expressed on the surface of tumor cells, and (PD-1), T impedes effective activation antigen-specific resulting in evasion cells from immune-mediated killing. Blocking PD-1/PD-L1 signaling pathway has been shown to be preventing immune evasion. blocking antibodies have garnered significant attention recent years within field treatments, given aforementioned mechanism. Furthermore, clinical research substantiated efficacy safety this immunotherapy across various tumors, offering renewed optimism for patients. However, challenges persist anti-PD-1/PD-L1 therapies, marked by limited indications emergence drug resistance. Consequently, identifying additional regulatory pathways molecules associated with implementing judicious combined treatments are imperative addressing intricacies mechanisms. This review briefly outlines structure molecule, emphasizing posttranslational modification mechanisms related targets. Additionally, a comprehensive overview landscape concerning post-translational modifications enhance outcomes broader spectrum patients presented based foundational research.
Язык: Английский
Процитировано
9
Biomedicines, Год журнала: 2024, Номер 12(2), С. 369 - 369
Опубликована: Фев. 5, 2024
Triple-negative breast cancer (TNBC) is a highly aggressive malignancy with pronounced immunogenicity, exhibiting rapid proliferation and immune cell infiltration into the tumor microenvironment. TNBC’s heterogeneity poses challenges to immunological treatments, inducing resistance mechanisms in Therapeutic modalities, including checkpoint inhibitors (ICIs) targeting PD-1, PD-L1, CTLA-4, are explored preclinical clinical trials. Promising results emerge from combining ICIs anti-TGF-β VISTA, hindering TNBC growth. cells employ complex evasion strategies involving interactions stromal cells, suppressing recognition through various cytokines, chemokines, metabolites. The recent focus on unraveling humoral cellular components aims disrupt crosstalk within This review identifies latest mechanisms, exploring potential targets for trials overcome enhance patient survival rates.
Язык: Английский
Процитировано
8
Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)
Опубликована: Янв. 2, 2025
Dysregulated energy metabolism has emerged as a defining hallmark of cancer, particularly evident in triple-negative breast cancer (TNBC). Distinct from other subtypes, TNBC exhibits heightened glycolysis and aggressiveness. However, the transcriptional mechanisms aerobic remains poorly understood. The Cancer Genome Atlas (TCGA) cohort was utilized to identify genes associated with glycolysis. role FOSL1 tumor growth cells confirmed through both loss-of-function gain-of-function experiments. subcutaneous xenograft model established evaluate therapeutic potential targeting TNBC. Additionally, chromatin immunoprecipitation luciferase reporter assays were employed investigate regulation glycolytic mediated by FOSL1. is identified pivotal glycolysis-related transcription factor Functional verification shows that enhances cells, evidenced glucose uptake, lactate production, extracellular acidification rates. Notably, promotes glycolysis-dependent manner, inhibiting 2-Deoxy-D-glucose markedly diminishes oncogenic effects Mechanistically, transcriptionally activates expression such SLC2A1, ENO1, LDHA, which further accelerate flux. Moreover, highly expressed doxorubicin (DOX)-resistant clinical samples cases progressive disease following neoadjuvant chemotherapy. Targeting proves effective overcoming chemoresistance DOX-resistant MDA-MB-231 cells. In summary, establishes robust link between carcinogenesis, positioning it promising target, especially context
Язык: Английский
Процитировано
1
Cancer Drug Resistance, Год журнала: 2025, Номер unknown
Опубликована: Фев. 8, 2025
Metabolic reprogramming within the tumor microenvironment (TME) plays a critical role in driving drug resistance gastrointestinal cancers (GI), particularly through pathways of fatty acid oxidation and glycolysis. Cancer cells often rewire their metabolism to sustain growth reshape TME, creating conditions such as nutrient depletion, hypoxia, acidity that impair antitumor immune responses. Immune TME also undergo metabolic alterations, frequently adopting immunosuppressive phenotypes promote progression reduce efficacy therapies. The competition for essential nutrients, glucose, between cancer compromises functions effector cells, T cells. Additionally, by-products like lactate kynurenine further suppress activity populations, including regulatory M2 macrophages. Targeting glycolysis presents new opportunities overcome improve therapeutic outcomes GI cancers. Modulating these key has potential reinvigorate exhausted shift toward phenotypes, enhance effectiveness immunotherapies other treatments. Future strategies will require continued research into metabolism, development novel inhibitors, clinical trials evaluating combination Identifying validating biomarkers be crucial patient stratification treatment monitoring. Insights may have broader implications across multiple types, offering avenues improving treatment.
Язык: Английский
Процитировано
1
Frontiers in Immunology, Год журнала: 2024, Номер 14
Опубликована: Янв. 11, 2024
Background We explored the characteristics of single-cell differentiation data in glioblastoma and established prognostic markers based on CRYAB to predict prognosis patients. Aberrant expression is associated with invasive behavior various tumors, including glioblastoma. However, specific role mechanisms are still unclear. Methods assessed RNA-seq microarray from TCGA GEO databases, combined scRNA-seq glioma patients GEO. Utilizing Seurat R package, we identified distinct survival-related gene clusters data. Prognostic pivotal genes were discovered through single-factor Cox analysis, a model was using LASSO stepwise regression algorithms. Moreover, investigated predictive potential these immune microenvironment their applicability immunotherapy. Finally, vitro experiments confirmed functional significance high-risk CRYAB. Results By analyzing ScRNA-seq data, 28 cell representing seven types. After dimensionality reduction clustering obtained four subpopulations within oligodendrocyte lineage trajectory. Using as marker for terminal-stage subpopulation, found that its poor prognosis. In demonstrated knocking out U87 LN229 cells reduced viability, proliferation, invasiveness. Conclusion The risk holds promise accurately predicting A comprehensive study would contribute understanding response Targeting may be beneficial
Язык: Английский
Процитировано
7
Journal of Translational Medicine, Год журнала: 2024, Номер 22(1)
Опубликована: Июль 30, 2024
Abstract During tumorigenesis and progression, the immune checkpoint programmed death-1 (PD-1) its ligand death ligand-1 (PD-L1) play critical roles in suppressing T cell-mediated anticancer responses, leading to T-cell exhaustion subsequent tumor evasion. Therefore, anti-PD-L1/PD-1 therapy has been an attractive strategy for treating cancer over past decade. However, overall efficacy of this approach remains suboptimal, revealing urgent need novel insights. Interestingly, increasing evidence indicates that both PD-L1 on cells PD-1 tumor-specific undergo extensive N-linked glycosylation, which is essential stability interaction these proteins, modification promotes In various preclinical models, targeting glycosylation PD-L1/PD-1 was shown significantly increase blockade therapy. Furthermore, deglycosylation strengthens signal intensity immunohistochemistry (IHC) assays, improving diagnostic therapeutic relevance protein. review, we provide overview regulatory mechanisms underlying as well crucial role PD-L1/PD-1-mediated addition, highlight promising implications clinical diagnosis treatment cancer. Our review identifies knowledge gaps sheds new light research field.
Язык: Английский
Процитировано
7
Small, Год журнала: 2024, Номер unknown
Опубликована: Авг. 3, 2024
Abstract Amplifying oxidative stress within tumor cells can effectively inhibit the growth and metastasis of triple‐negative breast cancer (TNBC). Therefore, development innovative nanomedicines that disrupt redox balance represents a promising yet challenging therapeutic strategy for TNBC. In this study, an amplifier, denoted as PBCH, comprising PdAg mesoporous nanozyme CaP mineralized layer, loaded with GSH inhibitor L‐buthionine sulfoximine (BSO), further surface‐modified hyaluronic acid target CD44, is introduced. acidic microenvironment, Ca 2+ initially released, thereby leading to mitochondrial dysfunction eventually triggering apoptosis. Additionally, BSO suppresses synthesis intracellular reduced amplifies level in cells. Furthermore, be activated by near‐infrared light induce photothermal photodynamic effects, causing burst ROS simultaneously promoting cell apoptosis via provoking immunogenic death. The high‐performance effects based on synergistic effect aforementioned multiple damage ablation, are validated TNBC animal models, declaring its potential safe effective anti‐tumor agent. proposed approach offers new perspectives precise efficient treatment
Язык: Английский
Процитировано
7