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Cited by 33HER2/EGFR in Cancer ResearchColorectal Cancer Treatments and StudiesLung Cancer Treatments and Mutations

The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.

Different proteome pattern of epidermal growth factor receptor–positive colorectal cancer cell lines that are responsive and nonresponsive to C225 antibody treatment

Open access
Skvortsov, Sergej, Sarg, Bettina, Loeffler-Ragg, Judith, Skvortsova, Ira, Lindner, Herbert, Werner Ott, Helmut, Lukas, Peter, Illmensee, Karl, Zwierzina, Heinz·2004·Molecular Cancer Therapeutics
DOI 10.1158/1535-7163.1551.3.12
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Abstract

The monoclonal antibody C225 directed against the epidermal growth factor receptor (EGFR) blocks downstream mitogenic signaling and is effective in patients with advanced colorectal cancer. Clinical data, however, suggest the presence of primary and secondary resistance mechanisms that are hardly understood. To define proteins involved in EGFR-triggered growth regulation and potential resistance mechanisms, we characterized the proteome profile of two colorectal cancer cell lines with a high expression of functional EGFR but a different response to treatment with C225. In Caco-2 and HRT-18, a complete saturation of EGFR was achieved after incubation with C225; whereas Caco-2 showed inhibition of proliferation, growth of HRT-18 was not suppressed. Using two-dimensional electrophoresis and subsequent mass spectrometry, we identified 14 proteins differentially expressed in both cell lines. All proteins are involved in metabolic pathways and malignant growth. Expression of enzymes such as ubiquitin carboxyl-terminal hydrolase isozyme 1, glutathione S-transferase P, and chloride intracellular channel protein 1 does not seem to interfere with the antiproliferative effect of anti-EGFR antibody. On the other hand, expression of proteins such as fatty acid binding protein and heat shock protein 27 might constitute strong antiapoptotic effects contributing to the nonresponse of HRT-18 to C225 treatment. Proteome-based investigations can help us better understand the complex protein interactions involved in EGFR signaling and its blockage by therapeutic monoclonal antibodies.

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Research works printed but not linked: 7

  1. Cunningham D, Humblet Y, Siena S, et al. Cetuximab (C225) alone or in combination with irinotecan (CPT-11) in patients with epidermal growth receptor (EGFR)-positive, irinotecan-refractory metastatic colorectal cancer (MCRC) [abstract 1012]. Proc Am Soc Clin Oncol 2003;22:252.
  2. Lutz MP, Schö ffski P, Folprecht G, et al. A phase I/II study of cetuximab (C225) plus irinotecan (CPT-11) and 24h infusional 5FU/folinic acid (FA) in the treatment of metastatic colorectal cancer (MCRC) expressing the epidermal growth factor receptor (EGFR) [abstract 265PD]. Ann Oncol 2002;13:73.
  3. Mendelsohn J, Shin DM, Donato N, et al. A phase I study of chimerized anti-epidermal growth factor receptor (EGFr) monoclonal antibody, C225, in combination with cisplatin (CDDP) in patients (PTS) with recurrent head and neck squamous cell carcinoma (SCC) [abstract 1502]. Proc Am Soc Clin Oncol 1999;18:389.
  4. Rubin MS, Shin DM, Pasmantier M, et al. Monoclonal antibody (MOAB) IMC-C225, an anti-epidermal growth factor receptor (EGFR), for patients (PTS) with EGFR-positive tumors refractory to or in relapse from previous therapeutic regimens [abstract 1860]. Proc Am Soc Clin Oncol 2000;19:498.
  5. Bonner JA, Ezekiel MP, Robert F, Meredith RF, Spencer SA, Waksal HW. Continued response following treatment with IMC-C225, an EGFr MoAb, combined with RT in advanced head and neck malignancies [abstract 5F]. Proc Am Soc Clin Oncol 2000;19:79.
  6. Janmaat ML, Kruyt FA, Rodriguez JA, Giaccone G. Response to epidermal growth factor receptor inhibitors in non-small cell lung cancer cells: limited antiproliferative effects and absence of apoptosis associated with persistent activity of extracellular signal-regulated kinase or Akt kinase pathways. Clin Cancer Res 2003;9:2316–26.
  7. Liu B, Fang M, Schmidt M, Lu Y, Mendelsohn J, Fan Z. Induction of apoptosis and activation of the caspase cascade by anti-EGF receptor monoclonal antibodies in DiFi human colon cancer cells do not involve the c-jun N-terminal kinase activity. Br J Cancer 2000;82:1991–9.

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Metadata

Authors
Skvortsov, S., Sarg, B., Loeffler-Ragg, J., Skvortsova, I., Lindner, H., Werner Ott, H., Lukas, P., Illmensee, K., & Zwierzina, H.
Affiliations
  • 1Internal Medicine, Departments of
  • Innsbruck Medical University (AT)
  • 2Radiotherapy-Radiooncology,
  • 3Gynaecology and Obstetrics and
ORCID
Venue
Molecular Cancer Therapeutics
Publisher
American Association for Cancer Research (AACR)
Published
2004-12-01
Volume
3
Issue
12
Pages
1551-1558
ISSN
  • 1535-7163 (ISSN-L)
  • 1538-8514
DOI
10.1158/1535-7163.1551.3.12
OpenAlex
W2188010225
Cited by
33
References
46
Citations by year
2025: 1 · 2023: 1 · 2021: 1 · 2020: 1 · 2019: 3 · 2012: 1
FWCI
2.08
Type
journal article
Language
en
Open access
Locations
  • Molecular Cancer Therapeutics (publishedVersion)
  • PubMed (publishedVersion)
Funders
Oesterreichische Nationalbank
Topics
  • Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
  • Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Keywords
epidermal growth factor receptor, colorectal cancer, anti-EGFR monoclonal antibody, treatment resistance, proteomic profiling, Caco-2 cells, EGFR signaling, glutathione S-transferase pi, fatty acid binding protein, HSP27, anti-apoptotic proteins, cell proliferation
MeSH terms
Cetuximab, Antibodies, Monoclonal, Antineoplastic Agents, Cell Survival, Humans, Neoplasm Proteins, Mass Spectrometry, Tumor Cells, Cultured, Colorectal Neoplasms, Electrophoresis, Gel, Two-Dimensional, Proteome, Cell Proliferation, Antibodies, Monoclonal, Humanized, ErbB Receptors

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