Small molecule inhibitors targeting the cancers

MedComm, Journal Year: 2022, Volume and Issue: 3(4)

Published: Oct. 13, 2022

Compared with traditional therapies, targeted therapy has merits in selectivity, efficacy, and tolerability. Small molecule inhibitors are one of the primary therapies for cancer. Due to their advantages a wide range targets, convenient medication, ability penetrate into central nervous system, many efforts have been devoted developing more small inhibitors. To date, 88 approved by United States Food Drug Administration treat cancers. Despite remarkable progress, cancer treatment still face obstacles, such as low response rate, short duration response, toxicity, biomarkers, resistance. better promote development targeting cancers, we comprehensively reviewed involved all agents pivotal drug candidates clinical trials arranged signaling pathways classification We discussed lessons learned from these agents, proper strategies overcome resistance arising different mechanisms, combination concerned Through our review, hoped provide insights perspectives research treatment.

Language: Английский

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Recent Developments in Layer‐by‐Layer Assembly for Drug Delivery and Tissue Engineering Applications

Advanced Healthcare Materials, Journal Year: 2023, Volume and Issue: 13(8)

Published: Dec. 20, 2023

Surfaces with biological functionalities are of great interest for biomaterials, tissue engineering, biophysics, and controlling processes. The layer-by-layer (LbL) assembly is a highly versatile methodology introduced 30 years ago, which consists assembling complementary polyelectrolytes or biomolecules in stepwise manner to form thin self-assembled films. In view its simplicity, compatibility molecules, adaptability any kind supporting material carrier, this technology has undergone major developments over the past decades. Specific applications have emerged different biomedical fields owing possibility load immobilize preserved bioactivity, use an extremely broad range carriers, modify film's mechanical properties via crosslinking. review, focus on recent regarding LbL films formed as 2D 3D objects drug delivery engineering. Possible vaccinology, biomimetic models, well bone cardiovascular engineering highlighted. addition, most technological field film construction, such high-content liquid handling machine learning, expected open new perspectives future LbL, presented.

Language: Английский

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An emerging paradigm of CXCL12 involvement in the metastatic cascade

Cytokine & Growth Factor Reviews, Journal Year: 2023, Volume and Issue: 75, P. 12 - 30

Published: Nov. 1, 2023

The chemokine CXCL12, also known as stromal cell-derived factor 1 (SDF1), has emerged a pivotal regulator in the intricate molecular networks driving cancer progression. As an influential tumor microenvironment, CXCL12 plays multifaceted role that spans beyond its traditional inducing invasion and metastasis. Indeed, been assigned functions related to epithelial-to-mesenchymal transition, cell stemness, angiogenesis, immunosuppression, all of which are currently viewed specialized biological programs contributing "metastatic cascade" among other hallmarks. Its interaction with cognate receptor, CXCR4, initiates cascade events not only shapes metastatic potential cells but defines niches within secondary organs support colonization. Given profound implications cascade, understanding mechanistic underpinnings is paramount importance for targeted elimination rate-limiting steps process. This review aims provide comprehensive overview current knowledge surrounding metastasis, especially interactions rationalizing therapeutic target.

Language: Английский

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Exploring CX3CR1 as a prognostic biomarker and immunotherapeutic target in sarcoma

Translational Oncology, Journal Year: 2025, Volume and Issue: 53, P. 102283 - 102283

Published: Jan. 20, 2025

Language: Английский

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Reshaping the immune microenvironment and reversing immunosenescence by natural products: prospects for immunotherapy in gastric cancer

Seminars in Cancer Biology, Journal Year: 2025, Volume and Issue: 110, P. 1 - 16

Published: Feb. 8, 2025

Language: Английский

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Pan-cancer characterization of C–C motif chemokine ligand 5 (CCL5) identifies its role as biomarker and therapeutic target

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 4, 2025

C–C Motif Chemokine Ligand 5 (CCL5) is known for its role in immune regulation and has been implicated cancer progression. However, expression prognostic significance pan-cancer require comprehensive evaluation. This study was initiated to decipher the of CCL5 genes. In silico analyses involving various online databases molecular experiments knockdown KIRC cell lines evaluated proliferation, colony formation, migration. significantly up-regulated several cancers. High correlated with poorer overall survival kidney renal carcinoma (KIRC) esophageal (ESCA) patients. Promoter hypomethylation elevated prognosis. mutations were rare; indicating driven by overexpression rather than genetic alterations. Positive correlations inhibitory MHC genes suggested CCL5's fostering an immunosuppressive tumor microenvironment. increased infiltration, particularly CD8 T cells macrophages. did not influence drug sensitivity. resulted reduced migration, underscoring critical dynamics. Our highlights progression prognosis, ESCA. modulating microenvironment potential as a therapeutic target warrant further investigation.

Language: Английский

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Multi-omics integration and machine learning identify and validate neutrophil extracellular trap-associated gene signatures in chronic rhinosinusitis with nasal polyps

Clinical Immunology, Journal Year: 2025, Volume and Issue: 275, P. 110473 - 110473

Published: March 13, 2025

Language: Английский

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Unraveling the triad of hypoxia, cancer cell stemness, and drug resistance

Journal of Hematology & Oncology, Journal Year: 2025, Volume and Issue: 18(1)

Published: March 18, 2025

In the domain of addressing cancer resistance, challenges such as limited effectiveness and treatment resistance remain persistent. Hypoxia is a key feature solid tumors strongly associated with poor prognosis in patients. Another significant portion development acquired drug attributed to tumor stemness. Cancer stem cells (CSCs), small cell subset self-renewal proliferative abilities, are crucial for initiation, metastasis, intra-tumoral heterogeneity. Studies have shown association between hypoxia CSCs context resistance. Recent studies reveal strong link stemness, which together promote survival progression during treatment. This review elucidates interplay CSCs, well their correlation therapeutic drugs. Targeting pivotal genes stemness holds promise novel therapeutics combat

Language: Английский

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Dual roles of CXCR4 (C-X-C motif chemokine receptor 4) in promoting entry of ebolavirus and targeting excessive glycoprotein for reticulophagic degradation to facilitate viral fitness.

Autophagy, Journal Year: 2025, Volume and Issue: unknown

Published: April 13, 2025

Ebola virus disease (EVD) caused by Zaire Ebolavirus (EBOV) infection is a major threat to public health in Africa and even worldwide, due its extremely high mortality rate. However, there are still no effective antiviral therapies that can completely cure EVD. A comprehensive understanding of virus-host interactions would be beneficial for developing new agents. Here, we showed CXCR4-induced macroautophagy/autophagy was internalized endosomes interacting with glycoprotein (GP) on viral particles during EBOV infection; this promoted the attachment entry, which reduced CXCR4 antagonist neutralizing antibody. We also found increased replication downregulating cytotoxic GP promote fitness instead influencing assembly factory. Mechanistically, excessive could hijack sorting transporting pathways their HGS, one key components ESCRT machinery; subsequently carried back endoplasmic reticulum CXCR4, where E3 ubiquitin ligase RNF185 recruited polyubiquitinate K27- K63-linked manner. Finally, polyubiquitinated degraded lysosomes via reticulophagy RETREG1 (reticulophagy regulator 1), an ATG3- ATG5-dependent Our findings revealed dual roles regulation life cycle, either acting as entry factor facilitate or targeting reticulophagic degradation, providing evidence hijacked host vesicular transportation system through efficient fitness.

Language: Английский

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Heterogeneity of primary and metastatic CAFs: From differential treatment outcomes to treatment opportunities (Review)

International Journal of Oncology, Journal Year: 2024, Volume and Issue: 64(5)

Published: April 4, 2024

Compared with primary tumor sites, metastatic sites appear more resistant to treatments and respond differently the treatment regimen. It may be due heterogeneity in microenvironment between tumors. Cancer‑associated fibroblasts (CAFs) are widely present stroma as key components of microenvironment. Primary CAFs (pCAFs) (mCAFs) heterogeneous terms source, activation mode, markers functional phenotypes. They can shape according organ, showing tumors metastases, which affect sensitivity these treatment. was hypothesized that understanding pCAFs mCAFs provide a glimpse into difference outcomes, providing new ideas for improving rate metastasis control various cancers.

Language: Английский

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