Together, results from our preclinical study using the in vivo mouse model in Fig. 7a–g prove that combining the FDA-approved anti-estrogen ICI 182,780 and sunitinib can increase the sunitinib sensitivity to better suppress RCC progression via altering the ERβ/ANGPT-2/Tie-2 pathway signaling. This evidence concerns the gene ESR2 and renal cell carcinoma.