Although this early work [37,38,39] was groundbreaking in dealing with the effects of endogenous NO on PDT outcomes in vivo, it left many questions unanswered, including: (i) whether the tumor itself (i.e., in addition to or instead of endothelium) can supply NO that might antagonize PDT; (ii) if so, which NOS isoform plays the major role; (iii) whether a basal level of NOS/NO is sufficient for PDT resistance or whether upregulation due to photodynamic stress plays a more important role; and (iv) the types of NO-mediated resistance signaling pathways that might be activated by PDT stress. Here, NOS2 is linked to neoplasm.