Lung cancer stem cells: a biological and clinical perspective

Lung cancer is the most lethal form of cancer in the world and despite significant therapeutic improvements that have been made, its survival rate still remains low. The latter is mainly due to the acquisition of resistance to systemic treatment regimens which, in turn, may be due to the presence of cancer stem cells (CSCs) within the primary tumors. CSCs constitute a subpopulation of cells that are highly tumorigenic and that exhibit biological properties similar to those of normal tissue stem cells, including an unlimited self-renewal capacity, an extensive proliferative capacity and a capacity to generate differentiated progeny. A better understanding of the signaling pathways that regulate lung CSC maintenance, proliferation, and tumorigenicity could thus lead to the design of improved approaches to lung cancer treatment. In this review we will discuss the current knowledge on lung CSCs, their biological properties and their putative clinical relevance. By employing currently available data, we will evaluate the prognostic value of several lung CSC markers. In addition, we will discuss the release of CSCs from tumor tissue into the blood circulation via epithelial-mesenchymal transition (EMT) as an important step towards acquiring a metastatic phenotype. Finally, we will provide an outlook into novel CSC-targeting approaches for achieving less invasive diagnostic procedures and improving long-term therapeutic options. Lung CSC research has gained considerable momentum to both basic and clinical applications, both aiming to identify a reliable panel of markers for lung CSCs and to clarify their function, with the final goal to develop a CSC-targeted therapy that will result in the complete elimination of CSCs for achieving significantly better long-time survival of lung cancer patients.