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Multiregion Quantification of Extracellular Signal-regulated Kinase Activity in Renal Cell Carcinoma.
Hoerner, Christian R; Massoudi, Rustin; Metzner, Thomas J; Stell, Laurel; O'Rourke, Jennifer J; Kong, Christina S; Liliental, Joanna E; Brooks, James D; Sabatti, Chiara; Leppert, John T; Fan, Alice C.
Afiliação
  • Hoerner CR; Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA; The Kidney Cancer Research Program, Stanford University School of Medicine, Stanford, CA, USA.
  • Massoudi R; The Kidney Cancer Research Program, Stanford University School of Medicine, Stanford, CA, USA; Department of Urology, Stanford University School of Medicine, Stanford, CA, USA.
  • Metzner TJ; The Kidney Cancer Research Program, Stanford University School of Medicine, Stanford, CA, USA; Department of Urology, Stanford University School of Medicine, Stanford, CA, USA; Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA.
  • Stell L; Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, USA.
  • O'Rourke JJ; Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA; The Kidney Cancer Research Program, Stanford University School of Medicine, Stanford, CA, USA.
  • Kong CS; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Liliental JE; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA; Translational Applications Service Center (TASC) and Translational Research and Applied Medicine (TRAM) Program, Stanford University School of Medicine, Stanford, CA, USA.
  • Brooks JD; The Kidney Cancer Research Program, Stanford University School of Medicine, Stanford, CA, USA; Department of Urology, Stanford University School of Medicine, Stanford, CA, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA; Bio-X, Stanford University, Stanford,
  • Sabatti C; Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA; Bio-X, Stanford University, Stanford, CA, USA; Department of Statistics, Stanford University, Stanford, CA, USA.
  • Leppert JT; The Kidney Cancer Research Program, Stanford University School of Medicine, Stanford, CA, USA; Department of Urology, Stanford University School of Medicine, Stanford, CA, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA; Bio-X, Stanford University, Stanford,
  • Fan AC; Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA; The Kidney Cancer Research Program, Stanford University School of Medicine, Stanford, CA, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA; Bio-X, Stanfor
Eur Urol Oncol ; 3(3): 360-364, 2020 06.
Article em En | MEDLINE | ID: mdl-31412000
To personalize treatment for renal cell carcinoma (RCC), it would be ideal to confirm the activity of druggable protein pathways within individual tumors. We have developed a high-resolution nanoimmunoassay (NIA) to measure protein activity with high precision in scant specimens (eg, fine needle aspirates [FNAs]). Here, we used NIA to determine whether protein activation varied in different regions of RCC tumors. Since most RCC therapies target angiogenesis by inhibiting the vascular endothelial growth factor (VEGF) receptor, we quantified phosphorylation of extracellular signal-regulated kinase (ERK), a downstream effector of the VEGF signaling pathway. In 90 ex vivo FNA biopsies sampled from multiple regions of 38 primary clear cell RCC tumors, ERK phosphorylation differed among patients. In contrast, within individual patients, we found limited intratumoral heterogeneity of ERK phosphorylation. Our results suggest that measuring ERK in a single FNA may be representative of ERK activity in different regions of the same tumor. As diagnostic and therapeutic protein biomarkers are being sought, NIA measurements of protein signaling may increase the clinical utility of renal mass biopsy and allow for the application of precision oncology for patients with localized and advanced RCC. PATIENT SUMMARY: In this report, we applied a new approach to measure the activity of extracellular signal-regulated kinase (ERK), a key cancer signaling protein, in different areas within kidney cancers. We found that ERK activity varied between patients, but that different regions within individual kidney tumors showed similar ERK activity. This suggests that a single biopsy of renal cell carcinoma may be sufficient to measure protein signaling activity to aid in precision oncology approaches.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma de Células Renais / MAP Quinases Reguladas por Sinal Extracelular / Neoplasias Renais Limite: Humans Idioma: En Revista: Eur Urol Oncol Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma de Células Renais / MAP Quinases Reguladas por Sinal Extracelular / Neoplasias Renais Limite: Humans Idioma: En Revista: Eur Urol Oncol Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos