Our current findings indicate that sunitinib triggers two resistance-promoting signaling pathways in RCC cells, both of which emanate from the ER stress response: a PERK-driven ER stress response that induces expression of the pro-tumorigenic cytokines IL-6, IL-8 and TNF-α, and a TRAF2-mediated NF-κB transcriptional survival program that protects tumor cells against cell death (Fig. 7). Here, TNF is linked to renal cell carcinoma.