Renal Cell Carcinoma Bone Metastasis

Epidermal Growth Factor Receptor Targeting

Kristy L. Weber, Michele Doucet, Janet E. Price

Research output: Contribution to journalArticle

Abstract

Renal cell carcinoma frequently metastasizes to the skeleton in the later stages of the disease. Patients with bone metastasis from renal cell carcinoma experience severe pain, neurologic compromise, and frequent pathologic fractures. These tumors are relatively resistant to chemotherapy and radiation, and the 5-year survival of patients is less than 10%. The epidermal growth factor receptor is overexpressed in human renal cell carcinoma and hypothesized to be a potential target in the treatment of bone metastasis. Using in vitro studies, it was shown that blockade of the epidermal growth factor receptor was effective in decreasing proliferation and receptor autophosphorylation of a human bone-derived renal cell carcinoma cell line. In an experimental nude mouse model, treatment with Taxol and protein tyrosine kinase inhibitor 166, a small molecule receptor tyrosine kinase inhibitor, blocked the growth of renal cell carcinoma in the tibia and resulted in decreased bone destruction. The use of protein tyrosine kinase inhibitor 166 and Taxol was cytostatic and nontoxic in long-term animal experiments. Epidermal growth factor receptor blockade is an exciting potential therapy for renal cell carcinoma bone metastasis in humans, but because it is cytostatic rather than cytotoxic, its optimal role may be as a supplement to cytotoxic chemotherapy. It ultimate role and its relationship to other therapeutic interventions remains to be elucidated and validated.

Original languageEnglish (US)
JournalClinical Orthopaedics and Related Research
Issue number415 SUPPL.
StatePublished - Oct 2003
Externally publishedYes

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Renal Cell Carcinoma
Epidermal Growth Factor Receptor
Neoplasm Metastasis
Bone and Bones
Cytostatic Agents
Protein Kinase Inhibitors
Paclitaxel
Protein-Tyrosine Kinases
Drug Therapy
Growth Inhibitors
Spontaneous Fractures
Receptor Protein-Tyrosine Kinases
Therapeutics
Tibia
Nude Mice
Skeleton
Nervous System
Radiation
Pain
Cell Line

ASJC Scopus subject areas

  • Surgery
  • Orthopedics and Sports Medicine

Cite this

Renal Cell Carcinoma Bone Metastasis : Epidermal Growth Factor Receptor Targeting. / Weber, Kristy L.; Doucet, Michele; Price, Janet E.

In: Clinical Orthopaedics and Related Research, No. 415 SUPPL., 10.2003.

Research output: Contribution to journalArticle

Weber, Kristy L. ; Doucet, Michele ; Price, Janet E. / Renal Cell Carcinoma Bone Metastasis : Epidermal Growth Factor Receptor Targeting. In: Clinical Orthopaedics and Related Research. 2003 ; No. 415 SUPPL.
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