Oncogene, Год журнала: 2025, Номер unknown
Опубликована: Март 1, 2025
Язык: Английский
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
Процитировано
120
Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 171, С. 116203 - 116203
Опубликована: Янв. 26, 2024
Tumor immunotherapy, an innovative anti-cancer therapy, has showcased encouraging outcomes across diverse tumor types. Among these, the PD-1/PD-L1 signaling pathway is a well-known immunological checkpoint, which significant in regulation of immune evasion by tumors. Nevertheless, considerable number patients develop resistance to anti-PD-1/PD-L1 rendering it ineffective long run. This research focuses on exploring factors PD-1/PD-L1-mediated immunotherapy. Initially, characterized its role facilitating evasion, emphasizing autoimmune homeostasis. Next, primary mechanisms PD-1/PD-L1-based immunotherapy are analyzed, including antigen deletion, T cell dysfunction, increased immunosuppressive cells, and alterations expression PD-L1 within cells. The possible ramifications altered metabolism, microbiota, DNA methylation also described. Finally, resolution strategies for dealing with discussed, placing particular emphasis personalized therapeutic approaches exploration more potent regimens.
Язык: Английский
Процитировано
41
Frontiers in Immunology, Год журнала: 2024, Номер 15
Опубликована: Март 28, 2024
Macrophages are the main component of tumor microenvironment, which differentiated from monocytes in blood and play an important role cancer development. Tumor-associated macrophages (TAMs) can promote growth, invasion, metastasis, resistance to anti–programmed death receptor 1 therapy by regulating programmed cell ligand expression interacting with other immune cells microenvironment. However, when activated properly, also anti-tumor enhancing phagocytosis cytotoxicity cells. TAM is associated poor prognosis drug patients treated immunotherapy, indicating that attractive targets for combined treatment. Combination targeting TAMs immunotherapy overcomes achieved excellent results some cancers, may be a promising strategy treatment future. Herein, we review recent findings on development, immunotherapy. We focus mainly macrophage-centered therapy, including strategies deplete reprogram TAMs, represent potential improving efficacy.
Язык: Английский
Процитировано
19
Circulation, Год журнала: 2024, Номер 149(22), С. 1729 - 1748
Опубликована: Март 15, 2024
Myocardial infarction (MI) and heart failure are associated with an increased incidence of cancer. However, the mechanism is complex unclear. Here, we aimed to test our hypothesis that cardiac small extracellular vesicles (sEVs), particularly mesenchymal stromal cell-derived sEVs (cMSC-sEVs), contribute link between post-MI left ventricular dysfunction (LVD)
Язык: Английский
Процитировано
18
Cancer Immunology Immunotherapy, Год журнала: 2024, Номер 73(6)
Опубликована: Май 2, 2024
In the malignant progression of tumors, there is deposition and cross-linking collagen, as well an increase in hyaluronic acid content, which can lead to extracellular matrix stiffness. Recent research evidence have shown that plays important role angiogenesis, cell proliferation, migration, immunosuppression, apoptosis, metabolism, resistance chemotherapeutic by alterations toward both secretion degradation. The clinical importance tumor-associated macrophage increasingly recognized, polarization a central series tumor immune processes through internal signal cascade, thus regulating progression. Immunotherapy has gradually become reliable potential treatment strategy for conventional chemotherapy advanced cancer patients, but presence exclusion major obstacle effectiveness, reasons their these approaches remain uncertain. Currently, lack exact mechanism on regulation stiffness exclusion. An in-depth understanding relationship between stiffness, polarization, will help reveal new therapeutic targets guide development methods patients. This review summarized different pathways molecular mechanisms involved provided available strategies address
Язык: Английский
Процитировано
17
International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(10), С. 5490 - 5490
Опубликована: Май 17, 2024
An immune checkpoint is a signaling pathway that regulates the recognition of antigens by T-cell receptors (TCRs) during an response. These checkpoints play pivotal role in suppressing excessive responses and maintaining homeostasis against viral or microbial infections. There are several FDA-approved inhibitors (ICIs), including ipilimumab, pembrolizumab, avelumab. ICIs target cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death 1 (PD-1), ligand (PD-L1). Furthermore, ongoing efforts focused on developing new with emerging potential. In comparison to conventional treatments, offer advantages reduced side effects durable responses. growing interest potential combining different chemotherapy, radiation therapy, targeted therapies. This article comprehensively reviews classification, mechanism action, application, combination strategies various cancers discusses their current limitations. Our objective contribute future development more effective anticancer drugs targeting checkpoints.
Язык: Английский
Процитировано
17
Theranostics, Год журнала: 2024, Номер 14(3), С. 1224 - 1240
Опубликована: Янв. 1, 2024
Background:The role of senescent cells in the tumor microenvironment (TME) is usually bilateral, and diverse therapeutic approaches, such as radiotherapy chemotherapy, can induce cellular senescence.Cellular interactions are widespread TME, reprogram immune metabolically by producing metabolites.However, how remodel metabolism TME remains unclear.This study aimed to explore precise targets enhance cells-induced anti-tumor immunity from a metabolic perspective. Methods:The vivo senescence model was induced 8 Gy×3 or cisplatin vitro 10 Gy-irradiation treatment.Metabonomic analysis ELISA assay on interstitial fluid were performed for metabolites screening.Marker expression cell infiltration analyzed flow cytometry.Cell co-culture system senescence-conditioned medium used crosstalk validation vitro.RNA sequencing rescue experiments conducted mechanism excavation.Immunofluorescence staining single-cell transcriptome profiling clinical validation.Results: We innovatively reveal landscape characterized with elevation adenosine.It attributed cell-induced CD73 upregulation tumor-associated macrophages (TAMs).CD73 TAMs evoked SASP-related pro-inflammatory cytokines, especially IL-6, regulated JAK/STAT3 pathway.Consistently, positive correlation between identified lung cancer specimens databases.Lastly, blocking background suppresses tumors activates CD8 + T cell-mediated antitumor immunity.Conclusions: expressed contributes significantly adenosine accumulation suggesting targeting novel synergistic strategy aging microenvironment.
Язык: Английский
Процитировано
16
Molecular Cancer, Год журнала: 2024, Номер 23(1)
Опубликована: Сен. 2, 2024
Programmed death receptor-1 (PD-1) and its ligand, programmed ligand-1 (PD-L1) are essential molecules that key in modulating immune responses. PD-L1 is constitutively expressed on various cells, epithelial cancer where it functions as a co-stimulatory molecule capable of impairing T-cell mediated Upon binding to PD-1 activated T-cells, the PD-1/PD-L1 interaction triggers signaling pathways can induce apoptosis or anergy, thereby facilitating escape tumors. In urological cancers, including bladder (BCa), renal cell carcinoma (RCC), prostate (PCa), upregulation has been demonstrated. It linked poor prognosis enhanced tumor evasion. Recent studies have highlighted significant role axis mechanisms cancers. The between T-cells further contributes immunosuppression by inhibiting activation proliferation. Clinical applications checkpoint inhibitors shown promising efficacy treating advanced significantly improving patient outcomes. However, resistance these therapies, either intrinsic acquired, remains challenge. This review aims provide comprehensive overview pathway We summarize regulatory mechanism underlying expression activity, genetic, epigenetic, post-transcriptional, post-translational modifications. Additionally, we discuss current clinical research inhibitors, their therapeutic potential, challenges associated with resistance. Understanding crucial for developing new strategies overcome limitations enhance immunotherapy.
Язык: Английский
Процитировано
16
Molecular Cancer, Год журнала: 2024, Номер 23(1)
Опубликована: Ноя. 21, 2024
Metabolic alterations, a hallmark of cancer, enable tumor cells to adapt their environment by modulating glucose, lipid, and amino acid metabolism, which fuels rapid growth contributes treatment resistance. In primary breast metabolic shifts such as the Warburg effect enhanced lipid synthesis are closely linked chemotherapy failure. Similarly, metastatic lesions often display distinct profiles that not only sustain but also confer resistance targeted therapies immunotherapies. The review emphasizes two major aspects: mechanisms driving in both how unique environments sites further complicate treatment. By targeting vulnerabilities at stages, new strategies could improve efficacy existing provide better outcomes for cancer patients.
Язык: Английский
Процитировано
16
Molecular Cancer, Год журнала: 2025, Номер 24(1)
Опубликована: Янв. 15, 2025
The last decade has witnessed unprecedented succusses with the use of immune checkpoint inhibitors in treating cancer. Nevertheless, proportion patients who respond favorably to treatment remained rather modest, partially due resistance. This fueled a wave research into potential mechanisms resistance which can be classified primary or acquired after an initial response. In current review, we summarize what is known so far about terms being tumor-intrinsic tumor-extrinsic taking account multimodal crosstalk between tumor, system compartment and other host-related factors.
Язык: Английский
Процитировано
3