Development and evaluation of a human CD47/HER2 bispecific antibody for Trastuzumab-resistant breast cancer immunotherapy

Drug Resistance Updates, Journal Year: 2024, Volume and Issue: 74, P. 101068 - 101068

Published: Feb. 13, 2024

Language: Английский

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Targeting undruggable phosphatase overcomes trastuzumab resistance by inhibiting multi-oncogenic kinases

Drug Resistance Updates, Journal Year: 2024, Volume and Issue: 76, P. 101118 - 101118

Published: July 14, 2024

Resistance to targeted therapy is one of the critical obstacles in cancer management. trastuzumab frequently develops treatment for HER2

Language: Английский

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Bioinformatics and computational studies of chabamide F and chabamide G for breast cancer and their probable mechanisms of action

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Aug. 27, 2024

Globally, the prevalence of breast cancer (BC) is increasing at an alarming level, despite early detection and technological improvements. Alkaloids are diverse chemical groups, many within this class have been reported as potential anticancer compounds. Chabamide F (F) chabamide G (G) two dimeric amide alkaloids found in a traditional medicinal plant, Piper chaba, possess significant cytotoxic effects. However, their scientific rationalization BC remains unknown. Here, we aimed to investigate molecular mechanisms for through silico approaches. From network pharmacology, identified 64 BC-related genes targets. GO KEGG studies showed that they were involved various biological processes mostly expressed pathways such RAS, PI3K-AKT, estrogen, MAPK, FoxO pathways. PPI analysis revealed SRC AKT1 hub genes, which play key roles tumorigenesis metastasis. Molecular docking strong binding affinity (− 10.7 kcal/mol) 9.4 − 11.7 AKT1, respectively, well acquisition vital residues inhibit them. Their long-term stability was evaluated using 200 ns dynamics simulation. The RMSD, RMSF, Rg, SASA analyses G-SRC G-AKT1 complexes excellently stable compared control, dasatinib, capivasertib, respectively. Additionally, PCA DCCM reduction residual correlation motions. By contrast, F-SRC complex greater than whereas it moderately with AKT1. MMPBSA demonstrated higher energies both compounds controls. In particular, energy 120.671 ± 16.997 130.437 19.111 kJ/mol, approximately twice high control molecules. Van der Waal polar solvation significantly contributed energy. Furthermore, them exhibited interactions site proteins. summary, study indicates these molecules could be ATP-competitive inhibitor allosteric

Language: Английский

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HER2 regulates autophagy and promotes migration in gastric cancer cells through the cGAS-STING pathway

Anti-Cancer Drugs, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 27, 2025

In gastric cancer, the relationship between human epidermal growth factor receptor 2 (HER2), cyclic GMP-AMP synthase—stimulator of interferon genes (cGAS-STING) pathway, and autophagy remains unclear. This study examines whether HER2 regulates in cancer cells via cGAS-STING signaling influencing key processes such as cell proliferation migration. Understanding this could uncover new molecular targets for diagnosis treatment. Through lentiviral transfection, counting kit-8 assays, colony formation, transwell migration, scratch siRNA, we found that overexpression suppresses inhibits autophagy, enhances migratory ability cells. contrast, knockdown activates promotes reduces We further observed inhibition using chloroquine (CQ) increases migration HER2-overexpressing Moreover, interfering with STING expression reversed defects caused by knockdown, underscoring critical role pathway HER2-regulated also revealed high is significantly associated poor prognosis. was identified an independent prognostic survival (hazard ratio, 1.942; 95% confidence interval, 1.06–3.54; P = 0.031). These results highlight importance HER2-driven regulation through progression its potential a therapeutic target.

Language: Английский

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CTGF (CCN2): a multifaceted mediator in breast cancer progression and therapeutic targeting

Cancer and Metastasis Reviews, Journal Year: 2025, Volume and Issue: 44(1)

Published: Feb. 13, 2025

Language: Английский

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TFAP2A-regulated CRNDE enhances colon cancer progression and chemoresistance via RIPK3 interaction

Functional & Integrative Genomics, Journal Year: 2025, Volume and Issue: 25(1)

Published: Feb. 15, 2025

Colon cancer (CC) is a common malignancy with rising incidence worldwide. Despite advances in treatment strategies, many patients still face poor prognosis due to the development of drug resistance. Long non-coding RNAs (lncRNAs) have emerged as important regulators various biological processes and been implicated progression. Among them, colorectal neoplasia differentially expressed (CRNDE) has drawn attention for its potential roles different cancers. However, specific functions CC remain unclear. In this study, we identified CRNDE highly CC, contributing tumor progression Mechanically, regulated by transcription factor TFAP2A. Additionally, inhibits pyroptosis, form programmed cell death, promoting ubiquitin-mediated degradation RIPK3, thereby reducing sensitivity cells 5-fluorouracil (5-FU). Our findings suggest that TFAP2A/CRNDE/RIPK3 axis plays critical colon chemoresistance, highlighting therapeutic targets improving outcomes.

Language: Английский

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The role of genetics and epigenetics in breast cancer: A comprehensive review of metastasis, risk factors, and future perspectives

Journal of Pharmaceutical Analysis, Journal Year: 2025, Volume and Issue: unknown, P. 101268 - 101268

Published: March 1, 2025

Language: Английский

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FOXM1 expression reverts aging chromatin profiles through repression of the senescence-associated pioneer factor AP-1

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

Published: March 25, 2025

Aging is characterized by changes in gene expression, some of which can drive deleterious cellular phenotypes and senescence. The transcriptional activation senescence genes has been mainly attributed to epigenetic shifts, but the chromatin accessibility its underlying mechanisms remain largely elusive natural aging. Here, we profiled human dermal fibroblasts (HDFs) from individuals with ages ranging neonatal octogenarian. We found that AP-1 binding motifs are prevalent elderly-specific accessible regions while neonatal-specific highly enriched for TEAD motifs. further show TEAD4 FOXM1 share a conserved regulatory landscape controlled not previously described age-dependent enhancer loses aging whose deletion drives Finally, demonstrate ectopic expression elderly cells partially resets youthful state due FOXM1's repressive function on several members complex, known trigger program. These results place at top hierarchical level remodeling required prevent Loss activity play key role authors repression AP-1-linked opening governs identify cis elements behind downregulation

Language: Английский

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Patient derived cancer organoids model the response to HER2-CD3 bispecific antibody (BsAbHER2) generated from hydroxyapatite gene delivery system

Cancer Letters, Journal Year: 2024, Volume and Issue: 597, P. 217043 - 217043

Published: June 12, 2024

Language: Английский

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Establishment and Validation of a Prognostic Risk Model Based on Adme-Related Genes in Breast Cancer

Published: Jan. 1, 2024

Language: Английский

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