Recently, Booth et al. reported that Pazopanib combined with PDE5i or ERBB1/2/4 inhibitor (afatinib) induced tumor cells (fresh PDX isolate of NSCLC) death via ER-induced stress by toxic autophagy and by affecting the chaperone activity in these cells an induction of ER stress-induced autophagy death . The ER stress-induced autophagy death is mediated via the pERK/eIF2α pathway. Furthermore, they also showed that pazopanib and BYL719 combination killed HCT116 cells that express a mutated active K-RAS protein and an activated PI3K-AKT-mTOR signaling pathway  indicating that pazopanib-dependent activation of the pERK/eIF2α pathway might be stress- and cell type-specific. Relative to these findings, our study focused on optimizing the effects of RT that induce microvascular dysfunction. Microvascular cells do not overexpress chaperones, a characteristic specific to tumor cells, or other mutation such as K-RAS, nor do they have constitutively active signaling pathways that drive proliferation. Therefore, the pERK/eIF2α pathway-mediated autophagy death may not occur in tumor-associated endothelial cells. The direct impact of SDRT and/or pazopanib on tumor cells, will be investigated in a future study.