Angiogenic signaling pathways and anti-angiogenic therapy for cancer

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

Published: May 11, 2023

Abstract Angiogenesis, the formation of new blood vessels, is a complex and dynamic process regulated by various pro- anti-angiogenic molecules, which plays crucial role in tumor growth, invasion, metastasis. With advances molecular cellular biology, biomolecules such as growth factors, chemokines, adhesion factors involved angiogenesis has gradually been elucidated. Targeted therapeutic research based on these molecules driven treatment to become promising strategy anti-tumor therapy. The most widely used agents include monoclonal antibodies tyrosine kinase inhibitors (TKIs) targeting vascular endothelial factor (VEGF) pathway. However, clinical benefit this modality still limited due several defects adverse events, acquired drug resistance, recurrence, lack validated biomarkers, impel further mechanisms angiogenesis, development multiple drugs combination therapy figure out how improve efficacy. Here, we broadly summarize signaling pathways discuss current challenges We also propose approaches efficacy provide perspective for

Language: Английский

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The molecular mechanisms and therapeutic strategies of EMT in tumor progression and metastasis

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: Sept. 8, 2022

Abstract Epithelial–mesenchymal transition (EMT) is an essential process in normal embryonic development and tissue regeneration. However, aberrant reactivation of EMT associated with malignant properties tumor cells during cancer progression metastasis, including promoted migration invasiveness, increased stemness, enhanced resistance to chemotherapy immunotherapy. tightly regulated by a complex network which orchestrated several intrinsic extrinsic factors, multiple transcription post-translational control, epigenetic modifications, noncoding RNA-mediated regulation. In this review, we described the molecular mechanisms, signaling pathways, stages tumorigenesis involved discussed dynamic non-binary its role metastasis. Finally, summarized challenges immunotherapy proposed strategies for therapy targeting EMT.

Language: Английский

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CRISPR/Cas9 therapeutics: progress and prospects

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

Published: Jan. 16, 2023

Abstract Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene-editing technology is the ideal tool of future for treating diseases by permanently correcting deleterious base mutations or disrupting disease-causing genes with great precision and efficiency. A variety efficient Cas9 variants derivatives have been developed to cope complex genomic changes that occur during diseases. However, strategies effectively deliver CRISPR system diseased cells in vivo are currently lacking, nonviral vectors target recognition functions may be focus research. Pathological physiological resulting from disease onset expected serve as identifying factors targeted delivery targets gene editing. Diseases both varied complex, choice appropriate methods different important. Meanwhile, there still many potential challenges identified when targeting CRISPR/Cas9 treatment. This paper reviews current developments three aspects, namely, type, vector, characteristics. Additionally, this summarizes successful examples clinical trials finally describes possible problems associated applications.

Language: Английский

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Cellular mechanotransduction in health and diseases: from molecular mechanism to therapeutic targets

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

Published: July 31, 2023

Abstract Cellular mechanotransduction, a critical regulator of numerous biological processes, is the conversion from mechanical signals to biochemical regarding cell activities and metabolism. Typical cues in organisms include hydrostatic pressure, fluid shear stress, tensile force, extracellular matrix stiffness or tissue elasticity, viscosity. Mechanotransduction has been expected trigger multiple such as embryonic development, repair regeneration. However, prolonged excessive stimulation can result pathological multi-organ fibrosis, tumorigenesis, cancer immunotherapy resistance. Although associations between normal homeostasis diseases have identified, regulatory mechanisms among different are not yet comprehensively illustrated, no effective therapies currently available targeting cue-related signaling. This review systematically summarizes characteristics typical conditions with updated evidence. The key effectors responding stimulations listed, Piezo channels, integrins, Yes-associated protein (YAP) /transcriptional coactivator PDZ-binding motif (TAZ), transient receptor potential vanilloid 4 (TRPV4). We also reviewed signaling pathways, therapeutic targets cutting-edge clinical applications related cues.

Language: Английский

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Targeting the PDGF/PDGFR signaling pathway for cancer therapy: A review

International Journal of Biological Macromolecules, Journal Year: 2022, Volume and Issue: 202, P. 539 - 557

Published: Jan. 21, 2022

Language: Английский

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Targeting Integrins for Cancer Therapy - Disappointments and Opportunities

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: March 9, 2022

Integrins mediate adhesive interactions between cells and their environment, including neighboring extracellular matrix (ECM). These heterodimeric transmembrane receptors bind ligands with globular head domains connect to the cytoskeleton through multi-protein at cytoplasmic tails. Integrin containing cell–matrix adhesions are dynamic force-responsive protein complexes that allow bidirectional mechanical coupling of environment. This allows sense modulate tissue mechanics regulates intracellular signaling impacting on cell faith, survival, proliferation, differentiation programs. Dysregulation these functions has been extensively reported in cancer associated tumor growth, invasion, angiogenesis, metastasis, therapy resistance. central role multiple hallmarks localization surface makes integrins attractive targets for therapy. However, despite a wealth highly encouraging preclinical data, targeting integrin adhesion clinical trials thus far failed meet expectations. Contributing factors therapeutic failure 1) variable expression, 2) redundancy function, 3) distinct roles various disease stages, 4) sequestering therapeutics by integrin-containing tumor-derived vesicles. Despite disappointing results, new promising approaches being investigated highlight potential as or prognostic biomarkers. Improvement delivery site via binding is emerging another successful approach may enhance both efficacy safety conventional therapeutics. In this review we provide an overview recent findings, discuss apparent disagreement consider opportunities exploit

Language: Английский

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Research progress on the interaction between oxidative stress and platelets: Another avenue for cancer?

Pharmacological Research, Journal Year: 2023, Volume and Issue: 191, P. 106777 - 106777

Published: April 19, 2023

Oxidative stress (OS) is a chemical imbalance between an oxidant and antioxidant, causing damage to redox signaling control or molecular damage. Unbalanced oxidative metabolism can produce excessive reactive oxygen species (ROS). These excess ROS cause drastic changes in platelet further affect function. It will also lead increase procoagulant phenotype cell apoptosis, which the risk of thrombosis. The creation subsequent activation, adhesion, recruitment are then encouraged auto-amplifying loop by produced from platelets. Meanwhile, cancer cells higher concentration due their fast high proliferation rate. However, result modification cellular macromolecules. formation its progression strongly associated with resulting In addition, platelets important part tumor microenvironment, there significant cross-communication cells. Cancer alter activation status platelets, RNA spectrum, proteome, other properties. "cloaking" providing physical protection，avoiding destruction shear attack immune cells, promoting invasion.We explored vicious circle interaction ROS, this review, we believe that play stimulative role growth metastasis through

Language: Английский

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A covalent peptide-based lysosome-targeting protein degradation platform for cancer immunotherapy

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 6, 2025

The lysosome-targeting chimera (LYTAC) strategy provided a very powerful tool for the degradation of membrane proteins. However, synthesis LYTACs, antibody-small molecule conjugates, is challenging. ability antibody-based LYTACs to penetrate solid tumor limited as well, especially cross blood-brain barrier (BBB). Here, we propose covalent chimeric peptide-based targeted platform (Pep-TACs) by introducing long flexible aryl sulfonyl fluoride group, which allows proximity-enabled cross-linking upon binding with protein interest. Pep-TACs facilitates target proteins through mechanism recycling transferrin receptor (TFRC)-mediated lysosomal endocytosis. Biological experiments demonstrate that can significantly degrade expression PD-L1 on cells, dendritic cells and macrophages, under acidic conditions, markedly enhance function T phagocytosis macrophages. Furthermore, both in anti-PD-1-responsive -resistant models, exert significant anti-tumor immune response. It noteworthy BBB prolong survival mice situ brain tumor. As proof-of-concept, this study introduces modular TFRC-based peptide protein, immunotherapy tumors. LYTAC strategies often face challenges penetration synthesis. authors introduce Pep-TACs, effectively degrades PD-L1. This approach suppresses growth, particularly

Language: Английский

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Extracellular matrix stiffness regulates colorectal cancer progression via HSF4

Journal of Experimental & Clinical Cancer Research, Journal Year: 2025, Volume and Issue: 44(1)

Published: Jan. 30, 2025

Abstract Background Colorectal cancer (CRC) has high incidence and mortality rates, with severe prognoses during invasion metastasis stages. Despite advancements in diagnostic therapeutic technologies, the impact of tumour microenvironment, particularly extracellular matrix (ECM) stiffness, on CRC progression is not fully understood. Methods This study included 107 patients. Tumour stiffness was assessed using magnetic resonance elastography (MRE), collagen ratio analysed Masson staining. cell lines were cultured matrices varying followed by transcriptome sequencing to identify stiffness-related genes. An HSF4 knockout model different ECM evaluate effects proliferation, migration, vitro vivo. Results significantly higher than normal tissue positively correlated content TNM staging. High-stiffness regulated functions signalling pathways. High (heat shock transcriptional factor 4) expression strongly associated poor prognosis. increased stages, its inhibited invasion, especially high-stiffness matrices. In vivo experiments confirmed that promoted growth metastasis, independent protein increase. Conclusions reveals promotes proliferation regulating EMT-related pathways through HSF4. could be valuable targets for prognostic assessment intervention CRC.

Language: Английский

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Homoharringtonine: mechanisms, clinical applications and research progress

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 30, 2025

Homoharringtonine is a natural alkaloid with significant pharmacological potential that has demonstrated promising efficacy in the treatment of hematological malignancies recent years. This article systematically reviews mechanisms Homoharringtonine, focusing on its key roles inducing apoptosis, inhibiting cell cycle progression, and reducing migration invasion. Additionally, HHT exhibits multiple biological activities, including immunomodulation, antiviral effects, anti-fibrotic properties, studies also revealing neuroprotective functions. In clinical trials, malignancies, particularly various types such as acute myeloid leukemia chronic leukemia. Despite antitumor effects observed applications, low bioavailability side remain major challenges limit widespread use. details latest research advancements aimed at enhancing drug delivery systems nanoparticles liposomes, well chemical modification strategies. These approaches not only improve HHT’s vivo but enhance targeting ability while toxicity to normal cells. Furthermore, combination other drugs presents broader prospects for treatment. By exploring diverse activities depth, this aims provide foundation developing novel therapeutic based products, thereby advancing application cancer fields.

Language: Английский

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