Abstract 3602: Antitumor effects of epidermal growth factor (EGF) and insulin-like growth factor (IGF) inhibitors in the treatment of metastatic renal cell carcinoma

Background: Renal cell carcinoma (RCC) is associated with mutation or loss of function of the von Hippel-Lindau gene resulting in hypoxia-inducible factor 1-alpha accumulation and production of growth factors involved in proliferation and angiogenesis. Radical nephrectomy remains the primary treatment option for two thirds of RCC patients who present with tumors confined to the kidney. However, approximately one half of patients will develop metastatic RCC. Treatment of RCC has been hampered by its resistance to most chemotherapy and hormonal therapy, although selected patients have long term remission from high dose of interleukin-2. Despite the recent availability of several active targeted agents in this disease, therapy is not curative. As a result, there is continued demand for improving therapy for metastatic disease to enhance both clinical benefits and patients overall survival. The EGF and IGF-1 pathways have been implicated as potential therapeutic targets in RCC. The objective of this study was to investigate the antitumor response to EGF and IGF inhibitors as a novel combination therapy in metastatic RCC. Methods: RCC cells lines (Caki-1 and Caki-2) were cultured in appropriate media supplemented with 10% FBS in a 5% CO2 incubator. Cells were treated for 24, 48, 72h, and 96h with different doses of EGFR (AG1478) and/or IGF-1R (AG1024) inhibitors (0-100 µM) given as single agent or in combination therapy. The epithelial cell proliferation was determined by AlamarBlue proliferation assay. Results: Both AG1478 and AG1024, given as single agent, decreased the epithelial cell proliferation of RCC human malignant cell lines (Caki-1 and Caki-2) (p