EGFR, HER2, and HER3 protein expression in paired primary tumor and lymph node metastasis of colorectal cancer

Ye, Peng; Li, Fanghua; Wei, Yuanyuan; Zhang, Yihao; Cui, Jianing; Dai, Rui; Chen, Hao; Xie, Jing; Cai, Peiling

doi:10.1038/s41598-022-17210-2

Cited by 4 publications

(1 citation statement)

References 54 publications

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“…Accordingly, kinase inhibitors targeting the elevated pathways are promising candidates against cancer [ 2 ]. Indeed, overexpression of the epidermal growth factor receptor (EGFR or ErbB1) and human epidermal growth factor receptor 2 (HER2 or ErbB2) belonging to the ErbB family of receptor tyrosine kinases (RTKs) is commonly detected in several solid tumors [ 3 , 4 , 5 , 6 ]. In addition, EGFR and HER2 have been validated as rational targets for cancer-related treatment [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, Biological Evaluation, and Molecular Dynamics Studies of Novel Lapatinib Derivatives

et al. 2022

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Co-expression of the epidermal growth factor receptor (EGFR, also known as ErbB1) and human epidermal growth factor receptor 2 (HER2) has been identified as a diagnostic or prognostic sign in various tumors. Despite the fact that lapatinib (EGFR/HER2 dual inhibitor) has shown to be successful, many patients do not respond to it or develop resistance for a variety of reasons that are still unclear. As a result, new approaches and inhibitory small molecules are still needed for EGFR/HER2 inhibition. Herein, novel lapatinib derivatives possessing 4-anilinoquinazoline and imidazole scaffolds (6a–l) were developed and screened as EGFR/HER2 dual inhibitors. In vitro and in silico investigations revealed that compound 6j has a high affinity for the ATP-binding regions of EGFR and HER2. All of the designed candidates were predicted to not penetrate the BBB, raising the expectation for the absence of CNS side effects. At 10 µM, derivatives possessing 3-chloro-4-(pyridin-2-ylmethoxy)aniline moiety (6i–l) demonstrated outstanding ranges of percentage inhibition against EGFR (97.65–99.03%) and HER2 (87.16–96.73%). Compound 6j showed nanomolar IC50 values over both kinases (1.8 nM over EGFR and 87.8 nM over HER2). Over EGFR, compound 6j was found to be 50-fold more potent than staurosporine and 6-fold more potent than lapatinib. A kinase selectivity panel of compound 6j showed poor to weak inhibitory activity over CDK2/cyclin A, c-MET, FGFR1, KDR/VEGFR2, and P38a/MAPK14, respectively. Structure–activity relationship (SAR) that were obtained with different substitutions were justified. Additionally, molecular docking and molecular dynamics studies revealed insights into the binding mode of the target compounds. Thus, compound 6j was identified as a highly effective and dual EGFR/HER2 inhibitor worthy of further investigation.

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Section: Introductionmentioning

confidence: 99%

Design, Synthesis, Biological Evaluation, and Molecular Dynamics Studies of Novel Lapatinib Derivatives

et al. 2022

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Advancements in Global Phosphoproteomics Profiling: Overcoming Challenges in Sensitivity and Quantification

Muneer,

Chen,

Chen

2024

Proteomics

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Protein phosphorylation introduces post‐genomic diversity to proteins, which plays a crucial role in various cellular activities. Elucidation of system‐wide signaling cascades requires high‐performance tools for precise identification and quantification of dynamics of site‐specific phosphorylation events. Recent advances in phosphoproteomic technologies have enabled the comprehensive mapping of the dynamic phosphoproteomic landscape, which has opened new avenues for exploring cell type‐specific functional networks underlying cellular functions and clinical phenotypes. Here, we provide an overview of the basics and challenges of phosphoproteomics, as well as the technological evolution and current state‐of‐the‐art global and quantitative phosphoproteomics methodologies. With a specific focus on highly sensitive platforms, we summarize recent trends and innovations in miniaturized sample preparation strategies for micro‐to‐nanoscale and single‐cell profiling, data‐independent acquisition mass spectrometry (DIA‐MS) for enhanced coverage, and quantitative phosphoproteomic pipelines for deep mapping of cell and disease biology. Each aspect of phosphoproteomic analysis presents unique challenges and opportunities for improvement and innovation. We specifically highlight evolving phosphoproteomic technologies that enable deep profiling from low‐input samples. Finally, we discuss the persistent challenges in phosphoproteomic technologies, including the feasibility of nanoscale and single‐cell phosphoproteomics, as well as future outlooks for biomedical applications.

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HER2-Positive Metastatic Colorectal Cancer

Robinson,

Messersmith,

Lentz

2024

Curr. Treat. Options in Oncol.

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EGFR, HER2, and HER3 protein expression in paired primary tumor and lymph node metastasis of colorectal cancer

Cited by 4 publications

References 54 publications

Design, Synthesis, Biological Evaluation, and Molecular Dynamics Studies of Novel Lapatinib Derivatives

Design, Synthesis, Biological Evaluation, and Molecular Dynamics Studies of Novel Lapatinib Derivatives

Advancements in Global Phosphoproteomics Profiling: Overcoming Challenges in Sensitivity and Quantification

HER2-Positive Metastatic Colorectal Cancer

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