Antibody–drug conjugates in cancer therapy: mechanisms and clinical studies

MedComm, Journal Year: 2024, Volume and Issue: 5(8)

Published: July 28, 2024

Abstract Antibody–drug conjugates (ADCs) consist of monoclonal antibodies that target tumor cells and cytotoxic drugs linked through linkers. By leveraging antibodies’ targeting properties, ADCs deliver into via endocytosis after identifying the antigen. This precise method aims to kill selectively while minimizing harm normal cells, offering safe effective therapeutic benefits. Recent years have seen significant progress in antitumor treatment with ADC development, providing patients new potent options. With over 300 explored for various indications some already approved clinical use, challenges such as resistance due factors like antigen expression, processing, payload emerged. review outline history their structure, mechanism action, recent composition advancements, selection, completed ongoing trials, mechanisms, intervention strategies. Additionally, it will delve potential novel markers, linkers, payloads, innovative action mechanisms enhance cancer The evolution has also led emergence combination therapy a approach improve drug efficacy.

Language: Английский

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The Biological Roles and Clinical Applications of the PI3K/AKT Pathway in Targeted Therapy Resistance in HER2-Positive Breast Cancer: A Comprehensive Review

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(24), P. 13376 - 13376

Published: Dec. 13, 2024

Epidermal growth factor receptor 2-positive breast cancer (HER2+ BC) is a highly invasive and malignant type of tumor. Due to its resistance HER2-targeted therapy, HER2+ BC has poor prognosis tendency for metastasis. Understanding the mechanisms underlying this developing effective treatments are major research challenges. The phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) pathway, which frequently altered in cancers, plays critical role cellular proliferation drug resistance. This signaling pathway activates various downstream pathways exhibits complex interactions with other networks. Given significance PI3K/AKT BC, several targeted drugs currently development. Multiple have entered clinical trials or gained market approval, bringing new hope therapy. However, therapies raise concerns related safety, regulation, ethics. Populations different races disease statuses exhibit varying responses treatments. Therefore, review, we summarize current knowledge on alteration biological roles as well applications perspectives, providing insights advancing BC.

Language: Английский

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Identification of a 7H-pyrrolo[2,3-d]pyrimidin derivatives as selective type II c-Met/Axl inhibitors with potent antitumor efficacy

Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: 156, P. 108187 - 108187

Published: Jan. 21, 2025

Language: Английский

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Inhibition of TFF3 synergizes with c-MET inhibitors to decrease the CSC-like phenotype and metastatic burden in ER+HER2+ mammary carcinoma

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 7, 2025

Abstract The interaction between HER2 and ERα signaling pathways contributes to resistance anti-estrogen HER2-targeted therapies, presenting substantial treatment challenges in ER-positive (ER+) HER2-positive (HER2+) mammary carcinoma (MC). Trefoil Factor-3 (TFF3) has been reported mediate both anti-HER2 targeted therapies ER+ ER+HER2+ MC, respectively. Herein, the function mechanism of TFF3 MC were delineated; novel combinatorial therapeutic strategies identified. Elevated expression promoted oncogenicity cells, including enhanced cell proliferation, survival, anchorage-independent growth, 3D cancer stem cell-like (CSC-like) phenotype, migration, invasion, xenograft growth. Targeting with an interfering RNA plasmid or a small-molecule inhibitor (AMPC) inhibited these oncogenic characteristics, highlighting potential targeting MC. Furthermore, high-throughput anti-cancer compound library screening revealed that AMPC preferentially synergized receptor tyrosine kinase c-MET inhibitors (c-METis) reduce survival CSC-like phenotype. combination c-METis also synergistically suppressed vivo growth cell-derived xenografts abrogated lung metastasis. Mechanistically, was observed activate through positive-feedback loop enhance phenotype Therefore, proof concept is provided herein antagonizing promising strategy inhibition for

Language: Английский

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Exploring Ketones in Chrysopogon zizanioides: A Computational Molecular Dynamic Approach to c-Met Modulation

Molecular Biotechnology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 19, 2025

Language: Английский

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Prognostic value of c-MET in oesophageal squamous cell carcinoma: a study based on the mRNA expression in TCGA database and a meta-analysis

Frontiers in Medicine, Journal Year: 2025, Volume and Issue: 12

Published: Feb. 26, 2025

Objective This study aims to assess the mesenchymal-epithelial transition factor’s (c-MET) prognostic value in oesophageal carcinoma (ESCA) through a meta-analysis and bioinformatics. Methods We analysed c-MET expression ESCA tissues using data from The Cancer Genome Atlas (TCGA) conducted evaluate its association with clinicopathological factors survival outcomes. included studies reporting hazard ratios (HRs) odds (ORs) for metastatic Results analysis revealed elevated ESCA, which was significantly correlated lymph node metastasis, tumour grade stage, though not overall (OS). In meta-analysis, 278 publications were identified, 89 duplicates removed. After screening, 176 articles excluded, leaving 13 full-text review. Of these, 5 lacked sufficient data, resulting 8 eligible total of 1,488 patients. Meta-analysis findings indicated that high associated worse OS (HR = 1.54, 95% confidence interval [CI]: 1.17–2.01; p 0.002), distant metastasis (OR 1.97, CI: 1.14–3.40; 0.02) advanced stage 2.23, 1.41–3.53; 0.0006). Conclusion High is poor prognosis disease highlighting potential as biomarker risk stratification. Further are needed confirm explore therapeutic implications.

Language: Английский

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Separation and purification of antioxidant peptides from Idesia polycarpa Maxim. cake meal and study of conformational relationship between them

Food Science & Nutrition, Journal Year: 2024, Volume and Issue: 12(9), P. 6206 - 6225

Published: July 10, 2024

Abstract In this study, peptides were isolated and purified from Idesia polycarpa Maxim. cake meal for the first time, with aim of discovering excellent antioxidant properties. Peptides using ultrafiltration dextran gel chromatography. Fractions significant activity identified by mass spectrometry (MS) screened characterized techniques, such as network pharmacology molecular docking. The results showed that CIPs‐I‐F2 fractions possessed activities, a total seven screened, main targets action including serine/threonine‐protein kinase AKT (AKT1), signal transducer activator transcription 3 (STAT3), matrix metalloproteinase 9 (MMP9), among which ISKPTWADF had highest binding energy to target. was synthesized in vitro solid‐phase synthesis dose‐dependent protective effect against hydrogen peroxide (H 2 O )‐induced oxidative damage model human hepatocellular carcinoma HepG2 cells, its active site on tryptophan indole ring at position 52N‐127H.

Language: Английский

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A new 1,2,3-triazole-indirubin hybrid suppresses tumor growth and pulmonary metastasis by mitigating the HGF/c-MET axis in hepatocellular carcinoma

Journal of Advanced Research, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 1, 2024

Hepatocellular carcinoma (HCC) is a fatal cancer that often diagnosed at the advanced stages which limits available therapeutic options. The interaction of HGF with c-MET (a receptor tyrosine kinase) results in activation subsequently triggers PI3K/Akt/mTOR axis. Overexpression HCC tissues has been demonstrated to contribute tumor progression and metastasis.

Language: Английский

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Fragment-based design and synthesis of coumarin-based thiazoles as dual c-MET/STAT-3 inhibitors for potential antitumor agents

Bioorganic Chemistry, Journal Year: 2024, Volume and Issue: 151, P. 107682 - 107682

Published: Aug. 6, 2024

Language: Английский

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Advances in Selective c-MET Kinase Inhibitors: Application of Fused [5,6]-Bicyclic Nitrogen-Containing Cores for Anticancer Drug Design

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 284, P. 117177 - 117177

Published: Dec. 20, 2024

Language: Английский

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