Abstract

COVID-19 and lung cancer are two severe pulmonary diseases that cause millions of deaths globally each year. Understanding the dysregulated signaling pathways between them can benefit treating the related patients. Recent studies suggest the critical role of reactive oxygen species (ROS) in both diseases, indicating an interplay between them. Here we reviewed references showing that ROS and ROS-associated signaling pathways, specifically via NRF2, HIF-1, and Nf-κB pathways, may bridge mutual impact between COVID-19 and lung cancer. As expected, typical ROS-associated inflammation pathways (HIF-1 and Nf-κB) are activated in both diseases. The activation of both pathways in immune cells leads to an overloading immune response and exacerbates inflammation in COVID-19. In lung cancer, HIF-1 activation facilitates immune escape, while Nf-κB activation in T cells suppresses tumor growth. However, the altered NRF2 pathway show opposite trends between them, NRF2 pathways exert immunosuppressive effects in both diseases, as it represses the immune response in COVID-19 patients while facilitates the immune escape of tumor cells. Furthermore, we summarized the therapeutic targets (e.g., phytochemicals) on these ROS pathways. In sum, our review focus on the understanding of ROS Signaling in COVID-19 and lung cancer, showing that modulating ROS signaling pathways may alleviate the potentially mutual impacts between COVID-19 and lung cancer patients.

Highlights

  • The 2019 coronavirus disease (COVID-19) is a pandemic acute respiratory disease breaking out in Wuhan and has spread throughout China and worldwide

  • Studies have highlighted the importance of reactive oxygen species (ROS) in COVID-19 and lung cancer progression and different metabolic mechanisms modulating the production and scavenging of ROS, which assists in the in-depth knowledge of disease pathophysiology

  • We focus on the several pathways involved in ROS-induced pathogenesis, including redox-sensitive transcription factor nuclear factor erythroid-2-related factor 2 (NRF2), the hypoxiainduced factors HIF-1a, and the Nuclear factor-kappa B (NF-kB) signaling

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Summary

Introduction

The 2019 coronavirus disease (COVID-19) is a pandemic acute respiratory disease breaking out in Wuhan and has spread throughout China and worldwide. Accumulating evidence suggests that the upregulated activity and expression of the NOX family play essential pathogenic roles in oxidative stress-induced lung cancer development through ROS production [29]. NOX level is upregulated in both diseases, which increases oxidative stress and exerts pathogenic effects, suggesting it can be a promising target for the treatment of both COVID-19 and lung cancer [34, 35].

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