ArticleProceedings of the National Academy of Sciences of the United States of America2016
Quantitative proteomics and phosphoproteomics on serial tumor biopsies from a sorafenib-treated HCC patient.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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39 citing papers in PubMed, 75 citations in OpenAlex.
- Phosphopeptidome Profiling of Human Plasma for Hepatocellular Carcinoma Biomarker Discovery.Journal of proteome research · 2026Article
- Enrichment of Phosphorylated and Glycosylated MHC Peptides for Mass Spectrometry-Based Neoantigen Analysis.Methods in molecular biology (Clifton, N.J.) · 2026Article
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- A stepwise and digital pattern of RSK phosphorylation determines the outcome of thymic selection.iScience · 2023Article
- Targeting casein kinase 1 for cancer therapy: current strategies and future perspectives.Frontiers in oncology · 2023Review
- The emerging role of mass spectrometry-based proteomics in drug discovery.Nature reviews. Drug discovery · 2022Review
- Comparative Assessment of Quantification Methods for Tumor Tissue Phosphoproteomics.Analytical chemistry · 2022Article
- Integrative proteogenomic characterization of hepatocellular carcinoma across etiologies and stages.Nature communications · 2022Review
- Computational analyses of mechanism of action (MoA): data, methods and integration.RSC chemical biology · 2022Review
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- Multi-omics data integration reveals novel drug targets in hepatocellular carcinoma.BMC genomics · 2021Article
- Underlying mechanism of sorafenib resistance in hepatocellular carcinoma: a bioinformatics study based on validated resistance-related genes.Journal of gastrointestinal oncology · 2021Article
- Dual Targeting of Sorafenib-Resistant HCC-Derived Cancer Stem Cells.Current oncology (Toronto, Ont.) · 2021Article
- Combined Inhibition of TGF-β1-Induced EMT and PD-L1 Silencing Re-Sensitizes Hepatocellular Carcinoma to Sorafenib Treatment.Journal of clinical medicine · 2021Article
- IL‑6 plays a crucial role in epithelial‑mesenchymal transition and pro‑metastasis induced by sorafenib in liver cancer.Oncology reports · 2021Article
- An omics perspective on drug target discovery platforms.Briefings in bioinformatics · 2020Article
- Time Course of Changes in Sorafenib-Treated Hepatocellular Carcinoma Cells Suggests Involvement of Phospho-Regulated Signaling in Ferroptosis Induction.Proteomics · 2020Article
- Severe metabolic alterations in liver cancer lead to ERK pathway activation and drug resistance.EBioMedicine · 2020Article
- Tumour evolution in hepatocellular carcinoma.Nature reviews. Gastroenterology & hepatology · 2020Review
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Authors and funding
11 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Compensatory signaling pathways in tumors confer resistance to targeted therapy, but the pathways and their mechanisms of activation remain largely unknown. We describe a procedure for quantitative proteomics and phosphoproteomics on snap-frozen biopsies of hepatocellular carcinoma (HCC) and matched nontumor liver tissue. We applied this procedure to monitor signaling pathways in serial biopsies taken from an HCC patient before and during treatment with the multikinase inhibitor sorafenib. At diagnosis, the patient had an advanced HCC. At the time of the second biopsy, abdominal imaging revealed progressive disease despite sorafenib treatment. Sorafenib was confirmed to inhibit MAPK signaling in the tumor, as measured by reduced ribosomal protein S6 kinase phosphorylation. Hierarchical clustering and enrichment analysis revealed pathways broadly implicated in tumor progression and resistance, such as epithelial-to-mesenchymal transition and cell adhesion pathways. Thus, we describe a protocol for quantitative analysis of oncogenic pathways in HCC biopsies and obtained first insights into the effect of sorafenib in vivo. This protocol will allow elucidation of mechanisms of resistance and enable precision medicine.
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