HER2 is the membrane receptor tyrosine kinase showing overexpression in several human malignancies, particularly breast cancer. HER2 overexpression causes the activation of Ras- MAPK and PI3K/Akt/ NF-κB cellular signal transduction pathways that lead to cancer development and progression. HER2 is, therefore, presumed as one of the key targets for the development of tumor-specific therapies. Several preclinical have been developed that function by inhibiting the HER2 tyrosine kinase activity through the prevention of the dimerization process. Most HER2 inhibitors act as ATP competitors and prevent the process of phosphorylation, and abort the cell cycle progression and proliferation. In this review, the clinical drug candidates and potent pre-clinical newly developed molecules are described, and the core chemical scaffolds typically responsible for anti-HER2 activity are deciphered. In addition, the monoclonal antibodies that are either used in monotherapy or in combination therapy against HER2-positive cancer are briefly described. The identified key moieties in this study could result in the discovery of more effective HER2-targeted anticancer drug molecules and circumvent the development of resistance by HER2-specific chemotherapeutics in the future.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.2174/0113816128283615231218094706 | DOI Listing |
Alzheimers Dement
December 2024
Indiana University School of Medicine, Indianapolis, IN, USA.
Background: The TREAT-AD centers aim to improve Alzheimer's Disease (AD) research by offering free, high-quality tools and technologies. Lyn is a tyrosine kinase that belongs to the Src family kinases. The expression of Lyn and its activity have been implicated in AD.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Indiana University School of Medicine, Indianapolis, IN, USA.
Background: Lyn kinase, a member of the Src family of tyrosine kinases, predominantly phosphorylates ITIM and ITAM motifs linked to immune receptors and adaptor proteins, and is emerging as a target for Alzheimer's disease (AD). The role of Lyn in TREM2-mediated microglial activation and phagocytosis, a critical pathway for clearing Aβ plaques, remains unclear and potent, selective, and brain penetrant Lyn inhibitors are unavailable. In this study, we report the characterization of Lyn kinase inhibitors from the literature as well as the establishment of an advanced virtual screening platform at the IUSM-Purdue-TREAT-AD center to identify new type II Lyn inhibitors suitable as molecular probes.
View Article and Find Full Text PDFHaematologica
January 2025
Hematology, Department of Translational and Precision Medicine, Sapienza University of Rome.
Not available.
View Article and Find Full Text PDFJ Exerc Rehabil
December 2024
Department of Human Health Care, Gyeongsang National University, Jinju, Korea.
Aging is associated with declines in memory function and significant change in gut microbiota. In this study, we investigated how exercise affects age-related memory decline and inflammation, and gut microbiota diversity. Bl6 mice were divided into control, control and exercise, old, and old and exercise groups.
View Article and Find Full Text PDFInt J Biol Sci
January 2025
Department of Urology, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, China.
Clear cell renal cell carcinoma (ccRCC) is one of the most common and aggressive malignancies of the urinary system. Despite being the first-line treatment for advanced ccRCC, vascular endothelial growth factor receptor inhibitors (VEGFRis) face significant limitations due to both initial and acquired resistance, which impede complete tumor eradication. Using a CRISPR/Cas9 library screening approach, was identified as a resistance-associated gene for three prevalent VEGFRis (Sunitinib, Axitinib, and Sorafenib).
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!