Oncogenèse pulmonaire : fondements moléculaires et implications thérapeutiques

Abstract

Non-small cell lung cancer represents the most prevalent form of lung cancer. Its biological understanding is currently framed by two principal models: the multistep model, which involves the progressive accumulation of genetic alterations often associated with tobacco exposure, and the oncogene addiction model, in which tumor growth is critically dependent on a single genetic driver. Advances in genomics have enabled more precise identification of mutations underlying tumor initiation and progression, as well as factors shaping therapeutic response. Certain precancerous lesions may progress to invasive disease through specific genetic events, modulation of the immune microenvironment, or external influences such as pollution. Emerging evidence indicates that pollutants can promote the emergence or activation of pre-existing tumor clones via inflammatory pathways. The oncogene addiction paradigm has facilitated the development of effective targeted therapies for defined patient subgroups, although therapeutic efficacy is frequently limited by mechanisms of resistance. Large-scale sequencing studies have further revealed the pronounced heterogeneity of lung tumors, characterized by complex clonal evolution shaped by treatment pressure, immune surveillance, and environmental factors. This heterogeneity likely underlies both intrinsic and acquired resistance to targeted agents. Within the framework of precision medicine, these insights provide a foundation for optimizing therapeutic strategies and may inform the development of novel approaches to prevention and longitudinal disease monitoring.