RNA demethylase ALKBH5 in cancer: from mechanisms to therapeutic potential

Journal of Hematology & Oncology, Год журнала: 2022, Номер 15(1)

Опубликована: Янв. 21, 2022

RNA demethylase ALKBH5 takes part in the modulation of N

Язык: Английский

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FTO in cancer: functions, molecular mechanisms, and therapeutic implications

Trends in cancer, Год журнала: 2022, Номер 8(7), С. 598 - 614

Опубликована: Март 25, 2022

Язык: Английский

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Small-molecule inhibitors, immune checkpoint inhibitors, and more: FDA-approved novel therapeutic drugs for solid tumors from 1991 to 2021

Journal of Hematology & Oncology, Год журнала: 2022, Номер 15(1)

Опубликована: Окт. 8, 2022

Abstract The United States Food and Drug Administration (US FDA) has always been a forerunner in drug evaluation supervision. Over the past 31 years, 1050 drugs (excluding vaccines, cell-based therapies, gene therapy products) have approved as new molecular entities (NMEs) or biologics license applications (BLAs). A total of 228 these were identified cancer therapeutics cancer-related drugs, 120 them classified therapeutic for solid tumors according to their initial indications. These evolved from small molecules with broad-spectrum antitumor properties early stage monoclonal antibodies (mAbs) antibody‒drug conjugates (ADCs) more precise targeting effect during most recent decade. extended indications other malignancies, constituting treatment system monotherapy combined therapy. However, available targets are still mainly limited receptor tyrosine kinases (RTKs), restricting development drugs. In this review, summarized indications, characteristics, functions. Additionally, RTK-targeted therapies immune checkpoint-based immunotherapies also discussed. Our analysis existing challenges potential opportunities may advance tumor future.

Язык: Английский

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Theranostic Fluorescent Probes

Chemical Reviews, Год журнала: 2024, Номер 124(5), С. 2699 - 2804

Опубликована: Фев. 29, 2024

The ability to gain spatiotemporal information, and in some cases achieve control, the context of drug delivery makes theranostic fluorescent probes an attractive intensely investigated research topic. This interest is reflected steep rise publications on topic that have appeared over past decade. Theranostic probes, their various incarnations, generally comprise a fluorophore linked masked drug, which released as result certain stimuli, with both intrinsic extrinsic stimuli being reported. release then signaled by emergence signal. Importantly, use appropriate fluorophores has enabled not only this emerging fluorescence marker for but also provided modalities useful photodynamic, photothermal, sonodynamic therapeutic applications. In review we highlight recent work particular focus are activated tumor microenvironments. We summarize efforts develop other applications, such neurodegenerative diseases antibacterials. celebrates diversity designs reported date, from discrete small-molecule systems nanomaterials. Our aim provide insights into potential clinical impact still-emerging direction.

Язык: Английский

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A Peritumorally Injected Immunomodulating Adjuvant Elicits Robust and Safe Metalloimmunotherapy against Solid Tumors

Advanced Materials, Год журнала: 2022, Номер 34(41)

Опубликована: Авг. 20, 2022

Clinical immunotherapy of solid tumors elicits durable responses only in a minority patients, largely due to the highly immunosuppressive tumor microenvironment (TME). Although rational combinations vaccine adjuvants with inflammatory cytokines or immune agonists that relieve immunosuppression represent an appealing therapeutic strategy against tumors, there are unavoidable nonspecific toxicities pleiotropy and undesired activation off-target cells. Herein, Zn2+ doped layered double hydroxide (Zn-LDH) based immunomodulating adjuvant, which not relieves but also robust antitumor immunity, is reported. Peritumorally injected Zn-LDH sustainably neutralizes acidic TME releases abundant , promoting pro-inflammatory network composed M1-tumor-associated macrophages, cytotoxic T cells, natural-killer Moreover, internalized by cells effectively disrupts endo-/lysosomes block autophagy induces mitochondrial damage, released activates cGas-STING signaling pathway induce immunogenic cell death, further promotes release tumor-associated antigens antigen-specific lymphocytes. Unprecedentedly, merely injection without using any agonists, significantly inhibits growth, recurrence, metastasis mice. This study provides bottom-up design potent adjuvant for cancer metalloimmunotherapy tumors.

Язык: Английский

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CD8+ T cell-intrinsic IL-6 signaling promotes resistance to anti-PD-L1 immunotherapy

Cell Reports Medicine, Год журнала: 2023, Номер 4(1), С. 100878 - 100878

Опубликована: Янв. 1, 2023

Although immune checkpoint inhibitors (ICIs) are established as effective cancer therapies, overcoming therapeutic resistance remains a critical challenge. Here we identify interleukin 6 (IL-6) correlate of poor response to atezolizumab (anti-PD-L1) in large clinical trials advanced kidney, breast, and bladder cancers. In pre-clinical models, combined blockade PD-L1 the IL-6 receptor (IL6R) causes synergistic regression tumors substantially improves anti-tumor CD8+ cytotoxic T lymphocyte (CTL) responses compared with anti-PD-L1 alone. Circulating CTLs from patients high plasma display repressed functional profile based on single-cell RNA sequencing, IL-6-STAT3 signaling inhibits classical differentiation vitro. tumor-bearing mice, CTL-specific IL6R deficiency is sufficient improve activity. Thus, both experimental evidence, agents targeting plausible partners for combination ICIs patients.

Язык: Английский

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T follicular helper cells in cancer

Trends in cancer, Год журнала: 2023, Номер 9(4), С. 309 - 325

Опубликована: Янв. 14, 2023

T follicular helper (Tfh) cells provide essential help to B for effective antibody-mediated immune responses. Although the crucial function of these CD4+ in infection and vaccination is well established, their involvement cancer only beginning emerge. Increased numbers Tfh cell-derived or cell-associated malignancies are often associated with an unfavorable outcome, whereas various solid organ tumor types non-lymphocytic origin, presence frequently coincides a better prognosis. We discuss recent advances understanding how cell crosstalk CD8+ secondary tertiary lymphoid structures (TLS) enhances antitumor immunity, but may also exacerbate immune-related adverse events (irAEs) such as autoimmunity during checkpoint blockade (ICB) immunotherapy.

Язык: Английский

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Crosstalk of disulfidptosis-related subtypes, establishment of a prognostic signature and immune infiltration characteristics in bladder cancer based on a machine learning survival framework

Frontiers in Endocrinology, Год журнала: 2023, Номер 14

Опубликована: Апрель 19, 2023

Background Bladder cancer (BLCA) is the most common malignancy of urinary tract. On other hand, disulfidptosis, a mechanism disulfide stress-induced cell death, closely associated with tumorigenesis and progression. Here, we investigated impact disulfidptosis-related genes (DRGs) on prognosis BLCA, identified various DRG clusters, developed risk model to assess patient prognosis, immunological profile, treatment response. Methods The expression mutational characteristics four DRGs were first analyzed in bulk RNA-Seq single-cell RNA sequencing data, IHC staining role BLCA progression, two clusters by consensus clustering. Using differentially expressed (DEGs) from these transformed ten machine learning algorithms into more than 80 combinations finally selected best algorithm construct prognostic signature (DRPS). We based this selection mean C-index three cohorts. Furthermore, explored differences clinical characteristics, landscape, immune infiltration, predicted efficacy immunotherapy between high low-risk groups. To visually depict value DRPS, employed nomograms. Additionally, verified whether DRPS predicts response patients utilizing Tumour Immune Dysfunction Rejection (TIDE) IMvigor 210 Results In integrated cohort, several gene that differed significantly overall survival (OS) tumor microenvironment. After integration clinicopathological features, showed robust predictive power. Based median score divided (LR) high-risk (HR) groups, LR group having better higher load being sensitive chemotherapy. Conclusion Our study, therefore, provides valuable tool further guide management tailor patients, offering new insights individualized treatment.

Язык: Английский

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Targeting oncogene and non-oncogene addiction to inflame the tumour microenvironment

Nature Reviews Drug Discovery, Год журнала: 2022, Номер 21(6), С. 440 - 462

Опубликована: Март 15, 2022

Язык: Английский

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Gut microbiome in modulating immune checkpoint inhibitors

EBioMedicine, Год журнала: 2022, Номер 82, С. 104163 - 104163

Опубликована: Июль 15, 2022

Gut microbiome has been increasingly recognized for its influence on a diverse array of human diseases including cancer, and may also the outcome cancer therapies. A prime example is seen in immunotherapy, which gut microbes determine therapeutic responses associated with immune checkpoint inhibitors (ICIs) preclinical models patient cohorts. This evidence hints that inter-individual variations microbiota account significant heterogeneity immunotherapeutic to ICIs. Understanding functional role regulating not only mucosal but systemic immunity critical move forward this era precision medicine. What's more, can be modified via several different strategies are essential efforts expanding immunotherapy efficacy. review summarizes latest knowledge about interactions between microbiome, host modulate implications translated into clinic.FundingThis study was supported by National Key R&D Program China (No. 2020YFA0509200/2020YFA0509203), RGC Theme-based Res Scheme Hong Kong (T21-705/20-N).

Язык: Английский

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