Abandoning the Notion of Non-Small Cell Lung Cancer

Non-small cell lung cancers (NSCLCs) represent 85% of lung tumors. NSCLCs encompass multiple cancer types, such as adenocarcinomas (LUADs), squamous cell cancers (LUSCs), and large cell cancers. Among them, LUADs and LUSCs are the largest NSCLC subgroups. LUADs and LUSCs appear sharply distinct at the transcriptomic level, as well as for cellular control networks. LUADs show distinct genetic drivers and divergent prognostic profiles versus LUSCs. Therapeutic clinical trials in NSCLC indicate differential LUAD versus LUSC response to treatments. Hence, LUAD and LUSC appear to be vastly distinct diseases at the molecular, pathological, and clinical level. Abandoning the notion of NSCLC may critically help in developing novel, more effective subtype-specific molecular alteration-targeted therapeutic procedures. Lung cancers are classified as small-cell (SCLC) or non-small cell (NSCLC). Such distinction reflects the different clinical presentation, disease course, and therapeutic options of the two subgroups.However, recent advances question the reason for categorizing together heterogeneous NSCLC subtypes such as adenocarcinomas (LUADs) and squamous cell carcinomas (LUSCs).Experimental evidence indicates that LUADs and LUSCs are sharply distinct at the transcriptomic level. Distinct genetic drivers, control networks, and prognostic profiles were identified in the two tumor subgroups. Therapeutic clinical trials in NSCLC indicated differential LUAD versus LUSC response to chemotherapy, kinase mutation-targeted treatments, and immune checkpoint inhibitors.LUAD and LUSC thus appear to be vastly distinct diseases at the molecular, pathological, and clinical level.