Lung cancer is a leading cause of cancer-related death worldwide, and the overall 5-year survival rate remains less than 14%. However, so far, the identification of lung CICs are still in dispute, and the results have yielded conflicting identification of lung CICs in different studies. Increasing evidence suggests that cancer stem cells (CSCs), also known as cancer initiating cells (CICs), play critical roles in tumor growth and resistance to conventional chemotherapies, and may be responsible for tumor metastasis and recurrence. Therefore, targeting of CSCs/CICs will be promising for lung cancer treatment. Although different biomarkers of CSCs/CICs, such as side population (ABC-G2), aldehyde dehydrogenase (ALDH) or CD133, have reported; unfortunately, these studies have yielded conflicting identification of CSCs/CICs in different types of cancer. The discrepancies of CSCs/CICs identification may due to the facts that identified CSCs/CICs have derived from well-developed tumors or artificial cell lines in most studies; furthermore, phenotypic and functional heterogeneity of clinical tumor samples and cell lines may exacerbate the divergence of CSCs/CICs in identification. Thus, to elucidate the possible origin of CSCs/CISs may help to understand the tumor formation in early stage and will be helpful to evaluate the candidate for therapeutic target, which will fulfill an unmet medical need in drug development in lung cancer therapy.
