Targeting angiogenesis in oncology, ophthalmology and beyond

Nature Reviews Drug Discovery, Journal Year: 2023, Volume and Issue: 22(6), P. 476 - 495

Published: April 11, 2023

Language: Английский

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Epigenetic regulation in the tumor microenvironment: molecular mechanisms and therapeutic targets

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 22, 2023

Abstract Over decades, researchers have focused on the epigenetic control of DNA-templated processes. Histone modification, DNA methylation, chromatin remodeling, RNA and noncoding RNAs modulate many biological processes that are crucial to development cancers. Dysregulation epigenome drives aberrant transcriptional programs. A growing body evidence suggests mechanisms modification dysregulated in human cancers might be excellent targets for tumor treatment. Epigenetics has also been shown influence immunogenicity immune cells involved antitumor responses. Thus, application therapy cancer immunotherapy their combinations may important implications Here, we present an up-to-date thorough description how modifications cell responses microenvironment (TME) epigenetics internally modify TME. Additionally, highlight therapeutic potential targeting regulators immunotherapy. Harnessing complex interplay between immunology develop therapeutics combine thereof is challenging but could yield significant benefits. The purpose this review assist understanding impact TME, so better immunotherapies can developed.

Language: Английский

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Emerging Sonodynamic Therapy‐Based Nanomedicines for Cancer Immunotherapy

Advanced Science, Journal Year: 2022, Volume and Issue: 10(2)

Published: Nov. 27, 2022

Cancer immunotherapy effect can be greatly enhanced by other methods to induce immunogenic cell death (ICD), which has profoundly affected as a highly efficient paradigm. However, these treatments have significant limitations, either causing damage of the immune system or limited superficial tumors. Sonodynamic therapy (SDT) ICD promote without affecting because its excellent spatiotemporal selectivity and low side effects. Nevertheless, SDT is still reactive oxygen species yield complex tumor microenvironment. Recently, some emerging SDT-based nanomedicines made numerous attractive encouraging achievements in field cancer due high immunotherapeutic efficiency. this cross-cutting research far from being widely explored huge professional barriers. Herein, characteristics microenvironment mechanisms are firstly systematically summarized. Subsequently, therapeutic mechanism fully summarized, advantages limitations discussed. The representative advances for further highlighted. Finally, application prospects challenges future clinical translation

Language: Английский

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Tumor microenvironment-mediated immune evasion in hepatocellular carcinoma

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 10, 2023

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and third leading cause of tumor-related mortality worldwide. In recent years, emergency immune checkpoint inhibitor (ICI) has revolutionized management HCC. Especially, combination atezolizumab (anti-PD1) bevacizumab (anti-VEGF) been approved by FDA as first-line treatment for advanced Despite great breakthrough in systemic therapy, HCC continues to portend a poor prognosis owing drug resistance frequent recurrence. The tumor microenvironment (TME) complex structured mixture characterized abnormal angiogenesis, chronic inflammation, dysregulated extracellular matrix (ECM) remodeling, collectively contributing immunosuppressive milieu that turn prompts proliferation, invasion, metastasis. coexists interacts with various cells maintain development It widely accepted dysfunctional tumor-immune ecosystem can lead failure surveillance. TME an external evasion consisting 1) cells; 2) co-inhibitory signals; 3) soluble cytokines signaling cascades; 4) metabolically hostile microenvironment; 5) gut microbiota affects microenvironment. Importantly, effectiveness immunotherapy largely depends on (TIME). Also, metabolism profoundly affect Understanding how progression will contribute better preventing HCC-specific overcoming already developed therapies. this review, we mainly introduce underlying role microenvironment, describe dynamic interaction microbiome, propose therapeutic strategies manipulate favor more effective immunotherapy.

Language: Английский

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JAK/STAT Signaling: Molecular Targets, Therapeutic Opportunities, and Limitations of Targeted Inhibitions in Solid Malignancies

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: March 24, 2022

JAK/STAT signaling pathway is one of the important regulatory cascades for myriad cellular processes initiated by various types ligands such as growth factors, hormones, and cytokines. The physiological regulated are immune regulation, cell proliferation, survival, apoptosis hematopoiesis myeloid non-myeloid cells. Dysregulation reported in immunological disorders, hematological other solid malignancies through oncogenic activation mutations receptors, downstream mediators, associated transcriptional factors STATs. STATs typically have a dual role when explored context cancer. While several members STAT family involved malignancies, however, few which include STAT3 STAT5 linked to tumor initiation progression. Other STAT1 STAT2 pivotal antitumor defense maintenance an effective long-term response evolutionarily conserved programs. effects persistent survival; proliferation invasion made ideal target drug development cancer therapy. Therefore, understanding intricate pathogenesis needs extensive research. A better functionally redundant roles JAKs may provide rationale improving existing therapies deleterious on normal cells identifying novel targets therapeutic intervention malignancies.

Language: Английский

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Tumor promoting roles of IL-10, TGF-β, IL-4, and IL-35: Its implications in cancer immunotherapy

SAGE Open Medicine, Journal Year: 2022, Volume and Issue: 10

Published: Jan. 1, 2022

Cytokines play a critical role in regulating host immune response toward cancer and determining the overall fate of tumorigenesis. The tumor microenvironment is dominated mainly by immune-suppressive cytokines that control effector antitumor immunity promote survival proliferation cells, which ultimately leads to enhanced growth. In addition heterogeneous cells present within milieu are significant source cytokines. These classified into broad range; however, most types, interleukin-10, transforming growth factor-β, interleukin-4, interleukin-35 consistently reported as help metastasis. emerging concern treatment hijacking restraining activity niche due highly environment. This review summarizes precise functions modulating contexture its implication developing effective immune-therapeutic approaches.Recent effort geared novel approaches faces challenges sustained mutations milieu. crucial an environment dictates critically covers aspects predominant such dictating tumorigenesis how targeting these can development better drug regimens for cancer.

Language: Английский

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Discovering dominant tumor immune archetypes in a pan-cancer census

Cell, Journal Year: 2021, Volume and Issue: 185(1), P. 184 - 203.e19

Published: Dec. 27, 2021

Language: Английский

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Metabolic Reprogramming of Colorectal Cancer Cells and the Microenvironment: Implication for Therapy

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(12), P. 6262 - 6262

Published: June 10, 2021

Colorectal carcinoma (CRC) is one of the most frequently diagnosed carcinomas and leading causes cancer-related death worldwide. Metabolic reprogramming, a hallmark cancer, closely related to initiation progression carcinomas, including CRC. Accumulating evidence shows that activation oncogenic pathways loss tumor suppressor genes regulate metabolic reprogramming mainly involved in glycolysis, glutaminolysis, one-carbon metabolism lipid metabolism. The abnormal program provides cells with abundant energy, nutrients redox requirements support their malignant growth metastasis, which accompanied by impaired flexibility microenvironment (TME) dysbiosis gut microbiota. crosstalk between cells, components TME intestinal microbiota further facilitates CRC cell proliferation, invasion metastasis leads therapy resistance. Hence, target dysregulated metabolism, microbiota, novel preventive therapeutic applications are required. In this review, dysregulation programs, molecular pathways, addressed. Possible strategies, inhibition immune CRC, as well modulation aberrant discussed.

Language: Английский

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Applications and clinical trial landscape using Toll-like receptor agonists to reduce the toll of cancer

npj Precision Oncology, Journal Year: 2023, Volume and Issue: 7(1)

Published: March 8, 2023

Abstract Toll-like receptors (TLRs), which serve as a bridge between innate and adaptive immunity, may be viable treatment targets. TLRs are the first line of defense against microbes activate signaling cascades that induce immune inflammatory responses. Patients with “hot” versus “cold” tumors respond more favorably to checkpoint inhibition, through their downstream effects, TLR agonists have potential convert “cold tumors” into “hot making in combination inhibitors, targets for cancer therapies. Imiquimod is topical TLR7 agonist, approved by FDA antiviral skin treatments. Other adjuvants used several vaccines including Nu Thrax, Heplisav, T-VEC, Cervarix. Many currently development both monotherapy inhibitors. In this review, we describe being evaluated clinically new therapies solid tumors.

Language: Английский

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Exploring dendrimer-based drug delivery systems and their potential applications in cancer immunotherapy

European Polymer Journal, Journal Year: 2022, Volume and Issue: 177, P. 111471 - 111471

Published: Aug. 1, 2022

Language: Английский

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