Targeting integrin pathways: mechanisms and advances in therapy

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

Published: Jan. 2, 2023

Abstract Integrins are considered the main cell-adhesion transmembrane receptors that play multifaceted roles as extracellular matrix (ECM)-cytoskeletal linkers and transducers in biochemical mechanical signals between cells their environment a wide range of states health diseases. Integrin functions dependable on delicate balance active inactive status via multiple mechanisms, including protein-protein interactions, conformational changes, trafficking. Due to exposure cell surface sensitivity molecular blockade, integrins have been investigated pharmacological targets for nearly 40 years, but given complexity sometimes opposite characteristics, targeting integrin therapeutics has challenge. To date, only seven drugs successfully marketed, abciximab, eptifibatide, tirofiban, natalizumab, vedolizumab, lifitegrast, carotegrast. Currently, there approximately 90 kinds integrin-based therapeutic or imaging agents clinical studies, small molecules, antibodies, synthetic mimic peptides, antibody–drug conjugates (ADCs), chimeric antigen receptor (CAR) T-cell therapy, agents, etc. A serious lesson from past drug discovery research efforts is successes rely both deep understanding integrin-regulatory mechanisms unmet needs. Herein, we provide systematic complete review all family members integrin-mediated downstream signal transduction highlight ongoing develop new therapies/diagnoses bench clinic. In addition, further discuss trend development, how improve success rate trials therapies, key points research, basic translational research.

Language: Английский

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Active targeting schemes for nano-drug delivery systems in osteosarcoma therapeutics

Journal of Nanobiotechnology, Journal Year: 2023, Volume and Issue: 21(1)

Published: March 22, 2023

Abstract Osteosarcoma, the most common malignant tumor of bone, seriously influences people’s lives and increases their economic burden. Conventional chemotherapy drugs achieve limited therapeutic effects owing to poor targeting severe systemic toxicity. Nanocarrier-based drug delivery systems can significantly enhance utilization efficiency chemotherapeutic through ligand modifications reduce occurrence adverse effects. A variety ligand-modified nano-drug have been developed for different schemes. Here we review biological characteristics main challenges current therapy OS, further elaborate on schemes selection osteosarcoma, which may provide new horizons development advanced targeted in future.

Language: Английский

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RGD peptide in cancer targeting: Benefits, challenges, solutions, and possible integrin–RGD interactions

Cancer Medicine, Journal Year: 2024, Volume and Issue: 13(2)

Published: Jan. 1, 2024

RGD peptide can be found in cell adhesion and signaling proteins, such as fibronectin, vitronectin, fibrinogen. peptides' principal function is to facilitate by interacting with integrin receptors on the surface. They have been intensively researched for use biotechnology medicine, including incorporation into biomaterials, conjugation medicinal molecules or nanoparticles, labeling imaging agents. peptides utilized specifically target cancer cells tumor vasculature engaging these integrins, improving drug delivery efficiency minimizing adverse effects healthy tissues. RGD-functionalized carriers are a viable option therapy this focused approach has demonstrated promise future. Writing review significantly influence how drugs developed future our understanding of peptide, finding knowledge gaps, fostering innovation, making design easier.

Language: Английский

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Role of RGD-binding Integrins in ovarian cancer progression, metastasis and response to therapy

Integrative Biology, Journal Year: 2025, Volume and Issue: 17

Published: Jan. 1, 2025

Integrins are transmembrane receptors that play a crucial role in cell adhesion and signaling by connecting the extracellular environment to intracellular cytoskeleton. After binding with specific ligands matrix (ECM), integrins undergo conformational changes transmit signals across membrane. The integrin-mediated bidirectional triggers various cellular responses, such as shape, migration proliferation. Irregular integrin expression activity closely linked tumor initiation, angiogenesis, motility, invasion, metastasis. Thus, understanding intricate regulatory mechanism is essential for slowing cancer progression preventing carcinogenesis. Among four classes of integrins, arginine-glycine-aspartic acid (RGD)-binding stand out most receptor subfamily its Dysregulation almost all RGD-binding promotes ECM degradation ovarian cancer, resulting carcinoma resistance therapy. Preclinical studies have demonstrated targeting these therapeutic antibodies ligands, RGD-containing peptides their derivatives, can enhance precision agents treating cancer. Therefore, development novel This review mainly discusses genes importance different subtypes, involvement RGD motif-containing proteins carcinoma, ongoing, completed, partially unsuccessful clinical trials agents, well existing limitations challenges, advancements made so far, potential strategies, directions future research field. Insight Box Integrin-mediated regulates migration, proliferation differentiation. Dysregulated promote growth dissemination. proper this complex delay prevent Notably, motifs an important evolution, small molecules motifs, target disrupt interactions ECM, thereby inhibiting migration. Altogether, highlights providing new insights into metastasis how been utilized develop effective treatment plans.

Language: Английский

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Peptide-Drug Conjugates: A New Hope for Cancer Management

Molecules, Journal Year: 2022, Volume and Issue: 27(21), P. 7232 - 7232

Published: Oct. 25, 2022

Cancer remains the leading cause of death worldwide despite advances in treatment options for patients. As such, safe and effective therapeutics are required. Short peptides provide advantages to be used cancer management due their unique properties, amazing versatility, progress biotechnology overcome peptide limitations. Several appealing peptide-based therapeutic strategies have been developed. Here, we an overview conjugates, better equivalents antibody-drug as next generation drugs required precise targeting, enhanced cellular permeability, improved drug selectivity, reduced toxicity efficient cancers. We discuss basic components conjugates release action, including cytotoxins from linker. also present peptide-drug under different stages clinical development well regulatory other challenges.

Language: Английский

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Therapeutic and Diagnostic Potential of Exosomes as Drug Delivery Systems in Brain Cancer

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(5), P. 1439 - 1439

Published: May 8, 2023

Cancer is designated as one of the principal causes mortality universally. Among different types cancer, brain cancer remains most challenging due to its aggressiveness, ineffective permeation ability drugs through blood–brain barrier (BBB), and drug resistance. To overcome aforementioned issues in fighting there an imperative need for designing novel therapeutic approaches. Exosomes have been proposed prospective “Trojan horse” nanocarriers anticancer theranostics owing their biocompatibility, increased stability, permeability, negligible immunogenicity, prolonged circulation time, high loading capacity. This review provides a comprehensive discussion on biological properties, physicochemical characteristics, isolation methods, biogenesis internalization exosomes, while it emphasizes diagnostic potential vehicle systems highlighting recent advances research field. A comparison activity effectiveness several exosome-encapsulated cargo including biomacromolecules underlines great supremacy over non-exosomal encapsulated delivery, accumulation, potency. Various studies cell lines animals give prominence exosome-based nanoparticles (NPs) promising alternative approach management cancer.

Language: Английский

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Skin Cancer Pathobiology at a Glance: A Focus on Imaging Techniques and Their Potential for Improved Diagnosis and Surveillance in Clinical Cohorts

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(2), P. 1079 - 1079

Published: Jan. 5, 2023

Early diagnosis is essential for completely eradicating skin cancer and maximizing patients' clinical benefits. Emerging optical imaging modalities such as reflectance confocal microscopy (RCM), coherence tomography (OCT), magnetic resonance (MRI), near-infrared (NIR) bioimaging, positron emission (PET), their combinations provide non-invasive data that may help in the early detection of cutaneous tumors surgical planning. Hence, they seem appropriate observing dynamic processes blood flow, immune cell activation, tumor energy metabolism, which be relevant disease evolution. This review discusses latest technological methodological advances techniques applied monitoring. In first instance, we will describe principle prospective applications most commonly used techniques, highlighting challenges opportunities implementation setting. We also highlight how complement molecular histological approaches sharpening characterization, laying ground more personalized patients.

Language: Английский

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Novel promising boron agents for boron neutron capture therapy: Current status and outlook on the future

Coordination Chemistry Reviews, Journal Year: 2024, Volume and Issue: 511, P. 215795 - 215795

Published: April 17, 2024

Language: Английский

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Skeletal muscle regeneration with 3D bioprinted hyaluronate/gelatin hydrogels incorporating MXene nanoparticles

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 265, P. 130696 - 130696

Published: March 6, 2024

Language: Английский

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Role of HIV-1 Tat Protein Interactions with Host Receptors in HIV Infection and Pathogenesis

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1704 - 1704

Published: Jan. 30, 2024

Each time the virus starts a new round of expression/replication, even under effective antiretroviral therapy (ART), transactivator viral transcription Tat is one first HIV-1 protein to be produced, as it strictly required for HIV replication and spreading. At this stage, most exits infected cells, accumulates in extracellular matrix exerts profound effects on both neighbor mostly innate adaptive immune systems. Through these effects, contributes acquisition infection, spreading progression AIDS untreated patients, or non-AIDS co-morbidities ART-treated individuals, who experience inflammation activation despite suppression. Here, we review role life cycle cells system, provide epidemiological experimental evidence importance targeting block residual expression replication. Finally, briefly vaccine studies showing that therapeutic intensifies ART, while its inclusion preventative may blunt escape from neutralizing antibodies early events acquisition.

Language: Английский

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