From Prognostic Marker to Therapeutic Agent: The Role of Nitric Oxide in Lung Cancer

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Abstract
Background: Nitric oxide (NO) is a gaseous free radical produced from L-arginine by the nitric oxide synthase (NOS) enzymes. NO exerts a dose-dependent biphasic effect on lung cancer development, angiogenesis, and dissemination. The widespread contribution of nitric oxide signaling to lung cancer biology has cast a spotlight on the identification of NO-based therapeutic approaches as well as the use of fractional exhaled NO (FeNO) as a prognostic biomarker of clinical control. However, the significance of lung cancer treatment and prognosis has not been fully elucidated. Objective: This narrative review gives an overview of NO in lung cancer, focusing on its therapeutic and prognostic implications. Results: FeNO may help to assess the complications associated with non-pharmacological treatments, including postoperative pneumonia and radiation pneumonitis. By contrast, the role of FeNO dynamics during pharmacological treatment is still largely unexplored due to the suppressive effect of chemotherapy on FeNO levels. The rise of immunotherapy may pave the way to a better evaluation of FeNO as a prognostic biomarker of treatment response. The dichotomous involvement of NO in lung cancer events has led to the adoption of several NO-centered treatments that are focused on both inhibiting and enhancing NO signaling. However, NO chemical and biological characteristics have hindered its implementation in clinical practice. Conclusions: In the coming years, the advancements in drug delivery systems may lead to more effective anti-cancer applications of NO by improving tumor targeting and minimizing the systemic side effects. Together, our findings emphasize the promising role of NO in lung cancer treatment, underscoring the challenges and avenues for future research.

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