Lung Cancer Stem Cells: Drivers of a Genetically and Histologically Complex Disease

Lung cancer is the leading cause of cancer-related deaths worldwide. The study of cancer stem cells (CSCs) may offer new ways to combat and control lung cancer growth. However, CSCs have not been precisely defined in human lung cancers. The resemblance of CSCs to normal cell counterparts likely varies with regard to multiple factors, including the genetic lesions initiating tumorigenesis and progression, the tumor microenvironment, and the cell of origin of the tumor-that is, the cell type in which oncogenesis occurs. Almost every epithelial cell type in the adult lung has been described with stem cell properties in some context, making links between "normal" lung stem cells and tumorigenic cells more complex. Studies in human lung cancer and mouse models aim to determine if cellular hierarchies exist within the predominant subtypes of lung cancer, and if so, how the genetic mutations present in the tumors modulate these hierarchies. CSCs and their links to metastasis, drug resistance, and immunotherapy could provide new opportunities for the assessment and treatment of lung cancer.