Therapeutic advances of targeting receptor tyrosine kinases in cancer DOI Creative Commons
Ciprian Tomuleasa, Adrian Bogdan Țigu, Raluca Munteanu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Aug. 14, 2024

Abstract Receptor tyrosine kinases (RTKs), a category of transmembrane receptors, have gained significant clinical attention in oncology due to their central role cancer pathogenesis. Genetic alterations, including mutations, amplifications, and overexpression certain RTKs, are critical creating environments conducive tumor development. Following discovery, extensive research has revealed how RTK dysregulation contributes oncogenesis, with many subtypes showing dependency on aberrant signaling for proliferation, survival progression. These findings paved the way targeted therapies that aim inhibit crucial biological pathways cancer. As result, RTKs emerged as primary targets anticancer therapeutic Over past two decades, this led synthesis validation numerous small molecule kinase inhibitors (TKIs), now effectively utilized treating various types. In manuscript we provide comprehensive understanding context We explored alterations specific receptors across different malignancies, special dedicated examination current inhibitors, highlighting potential therapies. By integrating latest evidence, seek elucidate pivotal biology efficacy inhibition promising treatment outcomes.

Language: Английский

The JAK/STAT signaling pathway: from bench to clinic DOI Creative Commons
Xiaoyi Hu, Jing Li,

Maorong Fu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Nov. 26, 2021

Abstract The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway was discovered more than a quarter-century ago. As fulcrum many vital cellular processes, the JAK/STAT constitutes rapid membrane-to-nucleus module induces expression various critical mediators cancer inflammation. Growing evidence suggests that dysregulation is associated with cancers autoimmune diseases. In this review, we discuss current knowledge about composition, activation, regulation pathway. Moreover, highlight role its inhibitors in

Language: Английский

Citations

1487
Adipose tissue and insulin resistance in obese DOI Open Access
Bulbul Ahmed, Rifat Sultana, Michael W. Greene

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2021, Volume and Issue: 137, P. 111315 - 111315

Published: Feb. 7, 2021

Currently, obesity has become a global health issue and is referred to as an epidemic. Dysfunctional obese adipose tissue plays pivotal role in the development of insulin resistance. However, mechanism how dysfunctional obese-adipose develops insulin-resistant circumstances remains poorly understood. Therefore, this review attempts highlight potential mechanisms behind obesity-associated Multiple risk factors are directly or indirectly associated with increased obesity; among them, environmental factors, genetics, aging, gut microbiota, diets prominent. Once individual becomes obese, adipocytes increase their size; therefore, tissues larger dysfunctional, recruit macrophages, then these polarize pro-inflammatory states. Enlarged release excess free fatty acids (FFAs), reactive oxygen species (ROS), cytokines. Excess systemic FFAs dietary lipids enter inside cells non-adipose organs such liver, muscle, pancreas, deposited ectopic fat, generating lipotoxicity. Toxic dysregulate cellular organelles, e.g., mitochondria, endoplasmic reticulum, lysosomes. Dysregulated organelles ROS pro-inflammation, resulting inflammation. Long term low-grade inflammation prevents from its action signaling pathway, disrupts glucose homeostasis, results dysregulation. Overall, long-term overnutrition develop into resistance chronic through lipotoxicity, creating clinical conditions. This also shows that liver most sensitive organ undergoing impairment faster than other organs, thus, hepatic primary event leads subsequent peripheral

Language: Английский

Citations

584
Regulatory mechanisms of immune checkpoints PD-L1 and CTLA-4 in cancer DOI Creative Commons
Hao Zhang, Ziyu Dai,

Wantao Wu

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2021, Volume and Issue: 40(1)

Published: June 4, 2021

Abstract The cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4)/B7 and programmed death 1 (PD-1)/ cell death-ligand (PD-L1) are two most representative immune checkpoint pathways, which negatively regulate T function during different phases of T-cell activation. Inhibitors targeting CTLA-4/B7 PD1/PD-L1 pathways have revolutionized immunotherapies for numerous cancer types. Although the combined anti-CTLA-4/B7 anti-PD1/PD-L1 therapy has demonstrated promising clinical efficacy, only a small percentage patients receiving or experienced prolonged survival. Regulation expression PD-L1 CTLA-4 significantly impacts treatment effect. Understanding in-depth mechanisms interplays could help identify with better immunotherapy responses promote their care. In this review, regulation is discussed at levels DNA, RNA, proteins, as well indirect biomarkers, localization within cell, drugs. Specifically, some potential drugs been developed to expressions high efficiency.

Language: Английский

Citations

357
Mechanisms governing activity-dependent synaptic pruning in the developing mammalian CNS DOI
Travis E. Faust, Georgia Gunner, Dorothy P. Schafer

et al.

Nature reviews. Neuroscience, Journal Year: 2021, Volume and Issue: 22(11), P. 657 - 673

Published: Sept. 20, 2021

Language: Английский

Citations

265
Evolving cognition of the JAK-STAT signaling pathway: autoimmune disorders and cancer DOI Creative Commons
Xue Chen,

Qinfan Yao,

Xinyu Gu

et al.

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

Published: May 19, 2023

Abstract The Janus kinase (JAK) signal transducer and activator of transcription (JAK-STAT) pathway is an evolutionarily conserved mechanism transmembrane transduction that enables cells to communicate with the exterior environment. Various cytokines, interferons, growth factors, other specific molecules activate JAK-STAT signaling drive a series physiological pathological processes, including proliferation, metabolism, immune response, inflammation, malignancy. Dysregulated related genetic mutations are strongly associated activation cancer progression. Insights into structures functions have led development approval diverse drugs for clinical treatment diseases. Currently, been developed mainly target commonly divided three subtypes: cytokine or receptor antibodies, JAK inhibitors, STAT inhibitors. And novel agents also continue be tested in preclinical studies. effectiveness safety each kind drug warrant further scientific trials before put being applications. Here, we review current understanding fundamental composition function pathway. We discuss advancements JAK-STAT–related pathogenic mechanisms; targeted therapies various diseases, especially disorders, cancers; newly inhibitors; challenges directions field.

Language: Английский

Citations

226
Chemotherapy: a double-edged sword in cancer treatment DOI

Nafiseh Behranvand,

Farzad Nasri,

Reza Zolfaghari Emameh

et al.

Cancer Immunology Immunotherapy, Journal Year: 2021, Volume and Issue: 71(3), P. 507 - 526

Published: Aug. 5, 2021

Language: Английский

Citations

220
CCL5/CCR5 axis in human diseases and related treatments DOI Creative Commons
Zhen Zeng,

Tianxia Lan,

Yuquan Wei

et al.

Genes & Diseases, Journal Year: 2021, Volume and Issue: 9(1), P. 12 - 27

Published: Aug. 26, 2021

To defense harmful stimuli or maintain the immune homeostasis, body produces and recruits a superfamily of cytokines such as interleukins, interferons, chemokines etc. Among them, act crucial regulators in systems. CCL5/CCR5 combination is known for facilitating inflammatory responses, well inducing adhesion migration different T cell subsets responses. In addition, recent studies have shown that interaction between CCL5 CCR5 involved various pathological processes including inflammation, chronic diseases, cancers infection COVID-19. This review focuses on how axis participates diseases their relevant signaling pathways regulation axis. Moreover, we highlighted gene therapy chemotherapy treating CCR5-related ongoing clinical trials. The barriers perspectives future application translational research were also summarized.

Language: Английский

Citations

216
Molecular Mechanism of Helicobacter pylori-Induced Gastric Cancer DOI Open Access
Majid Alipour

Journal of Gastrointestinal Cancer, Journal Year: 2020, Volume and Issue: 52(1), P. 23 - 30

Published: Sept. 14, 2020

Language: Английский

Citations

188
Role of JAK/STAT in Interstitial Lung Diseases; Molecular and Cellular Mechanisms DOI Open Access
Paula Montero, Javier Milara, Inés Roger

et al.

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(12), P. 6211 - 6211

Published: June 9, 2021

Interstitial lung diseases (ILDs) comprise different fibrotic disorders characterized by cellular proliferation, interstitial inflammation, and fibrosis. The JAK/STAT molecular pathway is activated under the interaction of a broad number profibrotic/pro-inflammatory cytokines, such as IL-6, IL-11, IL-13, among others, which are increased in ILDs. Similarly, several growth factors over-expressed ILDs, platelet-derived factor (PDGF), transforming β1 (TGF-β1), fibroblast (FGF) activate canonical or non-canonical pathways, indicates predominant role Between isoforms, it appears that JAK2/STAT3 predominant, initiating changes observed This review analyzes expression distribution isoforms ILDs tissue cell types related to fibroblasts alveolar epithelial type II cells activation. effect phosphorylation on processes, senescence, autophagy, endoplasmic reticulum stress, epithelial/fibroblast mesenchymal transition will be described. small molecules directed inhibit activation were assayed vitro vivo models pulmonary fibrosis, JAK inhibitors currently approved for myeloproliferative disorders. Recent evidence monoclonal antibodies block IL-6 used compassionate use attenuate excessive inflammation fibrosis SARS-CoV-2 virus. These altogether indicate an attractive target proven future clinical trials

Language: Английский

Citations

181
JAK-STAT Signalling Pathway in Cancer DOI Open Access
Andrew J. Brooks, Tracy L. Putoczki

Cancers, Journal Year: 2020, Volume and Issue: 12(7), P. 1971 - 1971

Published: July 20, 2020

n/a

Language: Английский

Citations

154