Research status and controversy on non-small cell lung cancer stem cells

Lung cancer is a major cause of cancer-related deaths worldwide. It can be divided into 2 main types, namely non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Most patients with NSCLC are diagnosed at an advanced stage, and current treatments have limited success. Moreover, relapsing tumors that often appear after surgical or drug treatment are particularly difficult to treat. The existence of cancer stem cells (CSCs) has been proposed as a key factor contributing to the development of resistance to therapy, recurrence and metastasis. Targeting CSCs is a potential strategy for eradicating tumors. However, due to the tumor-type specificity and cellular plasticity, the real clinical application of lung cancer stem cells (LCSCs) has not been realized. This review details the existing phenotypic markers of LCSCs and the limitations of their identification and summarizes the roles of the tumor microenvironment (TME) and epithelial-mesenchymal transition (EMT) in the existence and maintenance of LCSCs, as well as the contribution and controversy of cellular plasticity theory on LCSCs. It is expected that future research on LCSCs can solve the present problems, and approaches targeting LCSCs may be applied in the clinic as soon as possible.