IRF3 and neoplasm: We propose that pharmacological targeting of ERK1/2, which is already investigated in cancer patients with oncogenic RAS-dependent tumors (Lu et al., 2020), may also help attenuate the resistance to radio- and chemotherapy treatments mediated in part by STING-dependent pro-inflammatory factors, while retaining the anti-tumor activity of the IRF3/IFN-β branch of the pathway.