Endogenous modulators in lung cancer.

Abstract

This editorial aimed to consolidate current evidence on the role of major endogenous modulators-nitric oxide (NO), prostaglandins (PGs), thromboxanes (TXs), and endothelins (ETs) in the lung carcinogenesis, their receptor-specific actions, compensatory feedback mechanisms, and their role in tumor immune evasion and angiogenesis. We searched PubMed and Google Scholar with free-text and MeSH combinations of terms including "lung cancer", "nitric oxide", "inducible NOS", "COX-2", "prostaglandin E₂", "thromboxane A₂", "endothelin", "angiogenesis", and "immunosuppression". We examined English-language publications for mechanistic data, preclinical models, and clinical correlates, and synthesized findings from both animal and human tissue studies. We highlight here the dual, concentration-dependent actions of NO, PG-E2's immunosuppressive and pro-angiogenic actions <i>via</i> E-Prostanoid (EP2/EP4) receptors, thromboxane A₂'s pro-metastatic functions by thromboxane receptor signaling and interaction with platelet-tumor interaction, and the underappreciated roles of ETs. We also point to gaps in the existing literature on the differential roles of other prostanoid subtypes (<i>e.g.</i>, PGI2, PGD2), hypoxia-inducible factor-1α's role in regulation of inflammatory cascades, and clinical significance of compensatory upregulation of TX synthase following cycloxygenase-2 inhibition. These observations underscore the potential need for receptor-targeted therapies, biomarker-guided patient stratification, and improved translational models to inform the development of personalized anti-inflammatory interventions in lung cancer.