RESUMEN
Background and Objective: The global impact of cancer and cancer-related deaths has been a huge challenge and continues to be a setback in the health sector and beyond even in recent times. Cancer is the second leading cause of death globally with lung cancer (LC) being the second most prevalent malignancy and the leading cause of mortality amongst cancers in men and women worldwide. LC still constitutes a major burden despite recent advances in diagnostic and treatment tools. In this article, we review the trends in LC with an emphasis on non-small cell LC. We aimed to identify nuclear and mitochondrial genetic alterations, microbiome dysbiosis, and their significance in non-small cell LC tumorigenesis as well as its relevance in the future management of LCs. Methods: We identified studies for this review by searching the PubMed, Cochrane, Education Resources Information Center (ERIC), and Surveillance, Epidemiology, and End Results (SEER) databases for English-Language articles published from January 1, 2000 through to July 30, 2022, using keywords: lung cancer, non-small cell lung cancer, early detection, treatment, mitochondria, microbiome and epigenetics. Key Content and Findings: This review will highlight the genomic environment, mitochondrial and nuclear alterations that play a role in the etiopathogenesis of LC and its application in the progression as well as management of the disease. We also elaborate on current molecular tumor biomarkers and their therapeutic targets. Conclusions: LC remains the leading cause of cancer-related deaths globally with poor prognosis despite available treatment options and even recent advances in both diagnostic tools and management guidelines. Human nuclear and mitochondrial alterations clearly play a role in tumorigenesis and progressive genomic evolution is crucial in the early carcinogenesis of LC which is strongly influenced by host immune surveillance. It is imperative that more research and clinical trials be undertaken to appreciate an in-depth understanding of LC from the molecular level to facilitate the discovery of more targeted therapy and overall better management of LC.