Further supporting this notion, Stokes et al. (2023) demonstrated that treatment with multiple VEGFR-TKIs, including axitinib, cabozantinib, lenvatinib, and sunitinib, could activate PERK in 786-O RCC xenografts, implicating the unfolded protein response (UPR) as another potential mechanism of resistance[37]. This evidence concerns the gene EIF2AK3 and renal cell adenocarcinoma.