Involvement of Epidermal Growth Factor Receptor (EGFR) Signaling in Renal Cell Carcinoma Progression and Therapeutic Implication

Renal cell carcinoma (RCC) is the common type of kidney cancer linked to alteration of lipid, glucose, and amino acid metabolism. Early stage RCC has prognosis with overall 5-year survival rate of 90%, and the RCC has unfavorable prognosis when the disease metastasizes. Loss of or carrying mutated tumor suppressor gene VHL is the cause of HIF elevation leading to initiation of RCC. The epidermal growth factor receptor (EGFR) is a transmembrane protein, contributes to crucial role in cellular expansion, multiplication, and survival. EGFR overexpression in RCC is 40-80% and EGFR signaling pathway is dysregulated in various malignancies including RCC. RCC is not primarily governed by EGFR. Several critical pathways are dysregulated in RCC, that are mediated by EGFR including VHL-HIF pathway, PI3K/Akt/mTOR signalig, and VEGF-induced angiogenesis leading to tumor growth and RCC progression. Inhibition of angiogenesis was observed upon EGFR blockade. EGFR overexpression in RCC is linked to higher tumor grade, metastatic disease, worse prognosis, poor survival, and resistance to therapies. EGFR-mediated RCC progression is either due to higher EGF expression or elevation of EGFR in the cell membrane. Therefore, targeting EGFR in RCC is a robust strategy to inhibit EGFR-driven disease progression. In this review, we pointed out the potential role of EGFR in RCC and associated molecular mechanisms that are closely related to initiation and progression of RCC. Herein, we also highlighted the therapeutic implication of targeting the EGFR in RCC.