The NADPH oxidase (NOX) family includes seven members that are involved in a multitude of physiological functions. We and others have already shown that NOX could be the source of UVB-induced ROS generation. However, it has not yet been fully defined which members of the NOX family are responsible for UVB-induced ROS generation and what precise role NOX might play in UVB-induced carcinogenesis. 
We found that among NOX family members, NOX1 is over-activated after acute UVB-irradiation in a biphasic manner. Indeed, UVB irradiation induced an immediate strong activation of NOX1, which followed by a second more moderate increase in NOX1 activation some hours later. Specific inhibition of both early and late NOX1 activation using a new NOX1 peptide inhibitor (InhNOX1) led to increased NER efficiency and subsequently decreased apoptosis. In contrast, when only the second peak was blocked, the NER efficiency and apoptosis were both decreased. Tumor formation following chronic UVB irradiation was markedly decreased in SKH-1 hairless mice treated topically with InhNOX1 before each irradiation. To determine whether NOX1 inhibition had a more pronounced photo-protective effect in DNA repair deficient context, XPC-deficient mice treated with InhNOX1 were exposed to chronic UVB irradiation. Treatment with InhNOX1 resulted in a significant decrease in the number and size of tumors in these mice, too. Finally, to examine the anti-cancer progression effects of InhNOX1, XPC+/+ and XPC-/- mice were irradiated 22 and 13 weeks respectively and then treated topically with either scramble or InhNOX1. Results showed that InhNOX1 slowed down tumor growth significantly.
Altogether, these results suggest that:
1)	NOX1 plays a key role in the determination of the ultimate fate of UVB-irradiated cells through an intrinsic ROS priming function for quenching DNA damage and promoting survival,
2)	InhNOX1 may be a new approach to the prevention and treatment of cutaneous SCC in NER-proficient and -deficient patients.

Inhibition of NADPH oxidase-1 as a new approach for the prevention and treatment of cutaneous squamous cell carcinoma